PMC:1584416 JSON TXT 8 Projects

Annnotations TAB TSV DIC JSON TextAE

Id	Subject	Object	Predicate	Lexical cue
T2572	0-6	NN	denotes	Rescue
T84	0-6	NN	denotes	Rescue
T85	0-74	sentence	denotes	Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles
T86	7-9	IN	denotes	of
T2573	7-9	IN	denotes	of
T87	10-18	NN	denotes	Progeria
T2574	10-13805	JJ	denotes	Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles Compound Heterozygosity at theXpd Locus Abstract Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of “null” alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals. Effects of mutations in Xpd were investigated in mice. Compound heterozygotes of otherwise homozygous lethal alleles demonstrated interallelic complementation and partial phenotypic rescue of XPD-related disease symptoms. Introduction Interallelic complementation is defined as the ability of two differentially mutated alleles to function better together than either can on its own. Despite its near universality in lower organisms [1], its potential to contribute to clinical heterogeneity in human disease is seldom considered. Evidence of interallelic complementation at clinically relevant loci is limited to biochemical and cell-based studies of a handful of metabolic disorders with defects in enzymes including propinyl-CoA carboxylase [2], argininosuccinate lyase [3], galactose-1-phosphate uridylyltransferase [4], and methylmalonyl CoA mutase [5]. Compound heterozygotes are individuals carrying two different mutant alleles of the same gene. In the absence of a dominant (wild-type [wt]) allele, genetic interactions between recessive alleles (referred to here as “biallelic” effects) could result in different phenotypic outcomes including interallelic complementation. Although amelioration of disease symptoms by interallelic complementation would create an ascertainment bias in the clinic, the lack of evidence concerning interallelic complementation or other biallelic effects in human disease is likely caused by the difficulty in distinguishing such effects from environment and genetic background. XPD encodes one of the two helicase components of basal transcription/DNA repair factor IIH (TFIIH), a ten-subunit, multifunctional complex that is essential for multiple processes, including basal transcription initiation and DNA damage repair via the nucleotide excision repair (NER) pathway [6,7]. Alterations in XPD resulting in defective TFIIH function are associated with UV-sensitive, multisystem disorders including xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD) [8–10]. XP is marked by sun-induced pigmentation anomalies and a greater than 1,000-fold elevation in skin cancer risk. Severe cases can also present with growth retardation and primary neurodegeneration [11]. CS and TTD, on the other hand, are segmental progeroid disorders characterised by progressive post-natal growth failure and primary demyelination resulting in severe neurodysfunction, but without a clear cancer predisposition [12–15]. Patients with TTD additionally display hallmark sulphur-deficient brittle hair and nails and scaling skin [13], resulting from a basal transcription defect in specific cell types [16,17]. A related disorder with the cancer predisposition of XP combined with the neurodevelopmental complications of CS (XPCS), although rare, has also been described [18]. Many XPD mutations are associated with an exclusive disease phenotype (e.g., XPDR722W with TTD and XPDR683W with XP) and are thus viewed as causative of the corresponding syndromes. Alleles not associated exclusively with one disorder are considered “likely null” alleles [19,20]. Some of these alleles fail to support viability in a haploid Schizosaccharomyces pombe yeast strain with a null mutation in the XPD homologue rad15 and are thus considered devoid of significant biological activity [19]. This classification of alleles as either causative or null currently defines what we refer to as a “monoallelic” paradigm of XPD disease. However, the identification in recent years of XP complementation group D patients with atypical disease presentation, including symptoms of both XP and TTD [8], casts doubt on the ability of such a monoallelic paradigm to explain clinical heterogeneity in compound heterozygotes. Previously, we generated a TTD mouse model (XPDR722W) that phenocopies the human syndrome [15,21]. Here we report the generation of additional mutant Xpd alleles that fail to support viability on their own but nevertheless ameliorate TTD-associated premature segmental ageing, cutaneous features, cellular DNA repair capacity, and UV survival when present in a compound heterozygote state. Results Generation of Xpd Compound Heterozygotes We generated an Xpd knock-in allele with a point mutation encoding a single amino acid change (XPDG602D) found in the XPCS patient XPCS2 (Figure 1A–1C). mRNA expression from the targeted allele could be detected in embryonic stem cells by RT-PCR (Figure 1D), although expression was reduced approximately 5-fold relative to wt mRNA transcript levels as determined by Northern blotting of RNA from the testis of heterozygous animals (Figure 1E). Because patient XPCS2 was a hemizygote with mutant XPD protein (XPDG602D) expressed from a single allele, the corresponding mutation was expected to be viable in the homozygous state. However, homozygous mutant mice were not observed, neither amongst live births nor embryonic day 13.5 (E13.5) or E3.5 embryos (Table 1). The corresponding hypomorphic, mutant allele was thus designated as homozygous lethal (†XPCS). Homozygous lethality of the XPCS allele is likely due to reduced levels of expression of this essential protein as a result of gene targeting (Figure 1A) rather than to the mutation itself. Xpd ablation (XpdKO /KO ) is similarly incompatible with life beyond the earliest stages of embryogenesis [22]. Consistent with this interpretation, a different targeted Xpd mutation encoding XPDR683W, which is associated with XP in the homozygous state in humans, was similarly underexpressed and lethal in the homozygous state (designated as †XP allele) (Figure 1A–1C; Table 1; unpublished data). Also, a different targeting approach leading to the use of the native 3′UTR and removal of the neo gene resulted in normalisation of XpdXPCS mRNA levels and viable homozygous XpdXPCS/XPCS (XPDG602D/G602D) animals [23]. Figure 1 Targeting of the Mouse Xpd Gene (A) Schematic representation of the genomic structure and partial restriction map of the wt and targeted mouse Xpd loci. For the wt Xpd allele, shaded boxes represent coding regions of exons 12 and 19–23; the 3′UTR is represented by an open box. TGA indicates the translational stop codon; PolyA indicates the polyadenylation signal. For the XpdTTD targeted allele, the 194–base pair (bp) human XPD cDNA fragment fused to exon 22 is indicated as a striped box including the TTD (R722W) mutation indicated by a vertical arrow. Chicken β-globin exons 2 and 3 including the 3′UTR are indicated as black boxes with corresponding Roman numerals followed by the β-globin polyadenylation signal (PolyA*). For the Xpd†XP and Xpd†XPCS targeted alleles, vertical arrows indicate XPCS (G602D-encoding) and XP (R683W-encoding) mutations in exons 19 and 22, respectively. The unique 3′ probe located outside the targeting construct is marked by a thick black line. Restriction sites: B, BamHI; C, ClaI; E, EcoRI; H, HindIII; Hp, HpaI; Sf, SfiI. (B) Southern blot analysis of EcoRI-digested genomic DNA from wt, Xpd†XPCS/wt, and Xpd†XP/wt recombinant embryonic stem cell clones hybridised with the 3′ probe depicted in (A). The wt allele yields a 6.5-kilobase (kb) fragment, whereas both targeted Xpd†XP and Xpd†XPCS alleles yield a 5.1-kb fragment. (C) Genotyping of wt and targeted alleles by PCR using primers F2, R1, and mR as indicated in (A) yields fragments of 399 bp and 468 bp, respectively. (D) RT-PCR detection of mRNA expression originating from the targeted †XP and †XPCS alleles in embryonic stem cell clones using primers F1 (hybridising outside the targeting construct) and mR as indicated in (A) results in a 1,416-bp fragment. (E) Northern blot analysis of total RNA isolated from testis of homozygous wt and XpdTTD/TTD, heterozygous Xpd†XPCS/wt and XpdTTD/wt, and compound heterozygous Xpd†XPCS/TTD mice as indicated. Hybridisation with a 1.4-kb mouse Xpd cDNA probe detects mRNAs of 4, 3.3, and 2.7 kb from wt, Xpd†XPCS, and XpdTTD alleles, respectively. An ethidium bromide (EtBr)–stained gel showing the amount of total RNA loaded is shown below. Table 1 Frequency of Xpd†XP/†XP, Xpd†XPCS/†XPCS, and Compound Heterozygous Xpd†XP/†XPCS Embryos and Offspring “Null” Allele Can Alleviate Developmental Delay, Skin, and Hair Features of TTD To test the potential of a homozygous lethal “null” allele to nevertheless contribute to organismal phenotype, we combined an Xpd†XPCS allele with a viable XpdTTD allele by crossing the corresponding heterozygous animals. Similar to hemizygous TTD mice carrying one true Xpd knockout allele (XpdTTD/KO), compound heterozygous XpdTTD/†XPCS mice were born at the expected Mendelian frequencies. Expression from the Xpd†XPCS allele was also reduced in the testis of compound heterozygous animals, whereas expression from the XpdTTD allele was increased relative to wt by ~5-fold (Figure 1E). Because of a lack of available antibodies and the inability to distinguish amongst various mutant forms of XPD differing only by single amino acid substitutions, we were unable to ascertain the relative amount of XPD protein from the different alleles. Despite reduced levels of mRNA expression, the homozygous lethal Xpd†XPCS allele ameliorated multiple XpdTTD-associated disease symptoms in compound heterozygous XpdTTD/†XPCS animals including the hallmark brittle hair and cutaneous features fully penetrant in homo- and hemizygous TTD mice (Figure 2A–2C). In marked contrast to XpdTTD/TTD (and XpdTTD/KO) mice, which display complete hair loss in the first hair cycle and partial hair loss in subsequent cycles throughout their lives [21], compound heterozygous XpdTTD/†XPCS mice displayed some hair loss only during the first hair cycle and only locally at the back (Figure 2A). Scanning electron microscope analysis of XpdTTD/†XPCS hair revealed an almost normal appearance, with TTD-like features such as broken hairs found only at very low frequency (unpublished data). Amino acid analysis confirmed that cysteine levels in the hair of the XpdTTD/†XPCS mice were significantly higher than in XpdTTD/TTD animals, but remained below the wt level (Figure 2C). TTD hemizygotes (XpdTTD/KO) do not display significant differences in cutaneous features and longevity relative to homozygous XpdTTD/TTD mice [21]. Figure 2 Partial Rescue of TTD Cutaneous, Blood, and Developmental Phenotypes in Compound Heterozygous XpdTTD/†XPCS Mice (A) Photographs of 5-mo-old homozygous XpdTTD/TTD, compound heterozygous XpdTTD/†XPCS, and wt mice. Insets: images of first-round hair loss. (B) Histological analysis of the skin of XpdTTD/TTD, XpdTTD/†XPCS, and wt mice. TTD-associated acanthosis (thicker epidermis, indicated by solid vertical line), pronounced granular layer (indicated by arrows), and sebacious gland hyperplasia (indicated by dotted vertical line) were absent in the epidermis of XpdTTD/†XPCS and wt mice. Magnification 400×. (C) Cysteine content of hair from wt, XpdTTD/TTD, and XpdTTD/†XPCS mice. The p-value indicates significant differences between mutants and wt, as well as between XpdTTD/TTD and XpdTTD/†XPCS mice. Error bars indicate standard error of the mean (SEM). (D) Hematocrit values from blood of XpdTTD/TTD and XpdTTD/†XPCS mice. The p-values indicate the significance of the difference relative to wt. Error bars indicate SEM. (E) Body weights of developing XpdTTD/TTD and XpdTTD/†XPCS mice after weaning plotted as a percentage of the weight of age-matched control wt and heterozygote (hz) littermates (set at 100%). Error bars indicate SEM. Other prominent TTD features in the epidermis, including acanthosis (thickening of the layer of the nucleated cells), hyperkeratosis (prominent thickening of the cornified layer), and pronounced granular layer and sebacious gland hyperplasia (causing greasy appearance of the hair), were absent in the skin of XpdTTD/†XPCS mice, as established by blind microscopic examination of skin sections (Figure 2B). Furthermore, anaemia and developmental delay present in patients with TTD [24] and in XpdTTD/TTD mice [15] were both partially rescued in compound heterozygous XpdTTD/†XPCS mice (Figure 2D and 2E). Rescue of Progeroid
T88	19-21	IN	denotes	in
T89	22-41	NN	denotes	Trichothiodystrophy
T90	42-44	IN	denotes	by
T91	45-55	JJ	denotes	Homozygous
T93	56-62	JJ	denotes	Lethal
T94	63-66	NN	denotes	Xpd
T92	67-74	NNS	denotes	Alleles
T95	124-332	sentence	denotes	Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented.
T96	125-133	IN	denotes	Although
T98	134-142	NN	denotes	compound
T99	143-157	NN	denotes	heterozygosity
T100	157-159	,	denotes	,
T101	159-161	CC	denotes	or
T102	162-165	DT	denotes	the
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T104	175-177	IN	denotes	of
T105	178-181	CD	denotes	two
T107	182-191	JJ	denotes	different
T108	192-198	JJ	denotes	mutant
T106	199-206	NNS	denotes	alleles
T109	207-209	IN	denotes	of
T110	210-213	DT	denotes	the
T112	214-218	JJ	denotes	same
T111	219-223	NN	denotes	gene
T113	223-225	,	denotes	,
T97	225-227	VBZ	denotes	is
T115	228-234	JJ	denotes	common
T116	235-237	IN	denotes	in
T117	238-243	JJ	denotes	human
T119	244-253	JJ	denotes	recessive
T118	254-261	NN	denotes	disease
T120	261-263	,	denotes	,
T121	263-266	PRP$	denotes	its
T122	267-276	NN	denotes	potential
T123	277-279	TO	denotes	to
T124	280-286	VB	denotes	impact
T125	287-294	NN	denotes	disease
T126	295-302	NN	denotes	outcome
T127	303-306	VBZ	denotes	has
T128	307-310	RB	denotes	not
T129	311-315	VBN	denotes	been
T130	316-320	RB	denotes	well
T114	321-331	VBN	denotes	documented
T131	331-332	.	denotes	.
T132	332-487	sentence	denotes	This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background.
T133	333-337	DT	denotes	This
T134	338-340	VBZ	denotes	is
T135	341-345	RBS	denotes	most
T136	346-352	RB	denotes	likely
T137	353-360	IN	denotes	because
T138	361-363	IN	denotes	of
T139	364-367	DT	denotes	the
T141	368-376	JJ	denotes	inherent
T140	377-387	NN	denotes	difficulty
T142	388-390	IN	denotes	in
T143	391-405	VBG	denotes	distinguishing
T144	406-414	JJ	denotes	specific
T146	415-424	JJ	denotes	biallelic
T145	425-432	NNS	denotes	effects
T147	433-437	IN	denotes	from
T148	438-449	NNS	denotes	differences
T149	450-452	IN	denotes	in
T150	453-464	NN	denotes	environment
T151	465-467	CC	denotes	or
T152	468-475	JJ	denotes	genetic
T153	476-486	NN	denotes	background
T154	486-487	.	denotes	.
T155	487-666	sentence	denotes	We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models.
T156	488-490	PRP	denotes	We
T157	491-500	VBD	denotes	addressed
T158	501-504	DT	denotes	the
T159	505-514	NN	denotes	potential
T160	515-517	IN	denotes	of
T161	518-527	JJ	denotes	different
T163	528-537	JJ	denotes	recessive
T162	538-545	NNS	denotes	alleles
T164	546-548	TO	denotes	to
T165	549-559	VB	denotes	contribute
T166	560-562	IN	denotes	to
T167	563-566	DT	denotes	the
T169	567-576	JJ	denotes	enigmatic
T168	577-587	NN	denotes	pleiotropy
T170	588-598	VBN	denotes	associated
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T172	604-607	NN	denotes	XPD
T174	608-617	JJ	denotes	recessive
T173	618-627	NNS	denotes	disorders
T175	628-630	IN	denotes	in
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T178	640-652	JJ	denotes	heterozygous
T179	653-658	NN	denotes	mouse
T177	659-665	NNS	denotes	models
T180	665-666	.	denotes	.
T181	666-893	sentence	denotes	Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria.
T182	667-678	NNS	denotes	Alterations
T184	679-681	IN	denotes	in
T185	682-686	DT	denotes	this
T187	687-696	JJ	denotes	essential
T186	697-705	NN	denotes	helicase
T188	705-707	,	denotes	,
T189	707-711	IN	denotes	with
T190	712-721	NNS	denotes	functions
T191	722-724	IN	denotes	in
T192	725-729	CC	denotes	both
T194	730-733	NN	denotes	DNA
T193	734-740	NN	denotes	repair
T195	741-744	CC	denotes	and
T196	745-750	JJ	denotes	basal
T197	751-764	NN	denotes	transcription
T198	764-766	,	denotes	,
T183	766-772	VBP	denotes	result
T199	773-775	IN	denotes	in
T200	776-783	JJ	denotes	diverse
T201	784-795	NNS	denotes	pathologies
T202	796-803	VBG	denotes	ranging
T203	804-808	IN	denotes	from
T204	809-817	VBN	denotes	elevated
T206	818-820	NN	denotes	UV
T205	821-832	NN	denotes	sensitivity
T207	833-836	CC	denotes	and
T208	837-843	NN	denotes	cancer
T209	844-858	NN	denotes	predisposition
T210	859-861	IN	denotes	to
T211	862-873	VBN	denotes	accelerated
T213	874-883	JJ	denotes	segmental
T212	884-892	NN	denotes	progeria
T214	892-893	.	denotes	.
T215	893-1436	sentence	denotes	We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals.
T216	894-896	PRP	denotes	We
T217	897-903	VBP	denotes	report
T218	904-905	DT	denotes	a
T219	906-913	NN	denotes	variety
T220	914-916	IN	denotes	of
T221	917-926	JJ	denotes	biallelic
T222	927-934	NNS	denotes	effects
T223	935-937	IN	denotes	on
T224	938-948	JJ	denotes	organismal
T225	949-958	NN	denotes	phenotype
T226	959-971	JJ	denotes	attributable
T227	972-974	IN	denotes	to
T228	975-987	NNS	denotes	combinations
T229	988-990	IN	denotes	of
T230	991-1000	JJ	denotes	recessive
T232	1001-1004	NN	denotes	Xpd
T231	1005-1012	NNS	denotes	alleles
T233	1012-1014	,	denotes	,
T234	1014-1023	VBG	denotes	including
T235	1024-1027	DT	denotes	the
T236	1028-1037	NN	denotes	following
T237	1037-1039	:	denotes	:
T238	1039-1040	-LRB-	denotes	(
T239	1040-1041	LS	denotes	i
T241	1041-1042	-RRB-	denotes	)
T242	1043-1046	DT	denotes	the
T240	1047-1054	NN	denotes	ability
T243	1055-1057	IN	denotes	of
T244	1058-1068	JJ	denotes	homozygous
T246	1069-1075	JJ	denotes	lethal
T247	1076-1079	NN	denotes	Xpd
T245	1080-1087	NNS	denotes	alleles
T248	1088-1090	TO	denotes	to
T249	1091-1101	VB	denotes	ameliorate
T250	1102-1103	DT	denotes	a
T251	1104-1111	NN	denotes	variety
T252	1112-1114	IN	denotes	of
T253	1115-1122	NN	denotes	disease
T254	1123-1131	NNS	denotes	symptoms
T255	1132-1136	WRB	denotes	when
T257	1137-1142	PRP$	denotes	their
T259	1143-1152	JJ	denotes	essential
T260	1153-1158	JJ	denotes	basal
T261	1159-1172	NN	denotes	transcription
T258	1173-1181	NN	denotes	function
T262	1182-1184	VBZ	denotes	is
T256	1185-1193	VBN	denotes	supplied
T263	1194-1196	IN	denotes	by
T264	1197-1198	DT	denotes	a
T266	1199-1208	JJ	denotes	different
T267	1209-1216	NN	denotes	disease
T269	1216-1217	HYPH	denotes	-
T268	1217-1224	VBG	denotes	causing
T265	1225-1231	NN	denotes	allele
T270	1231-1233	,	denotes	,
T271	1233-1234	-LRB-	denotes	(
T272	1234-1236	LS	denotes	ii
T274	1236-1237	-RRB-	denotes	)
T275	1238-1250	JJ	denotes	differential
T276	1251-1264	JJ	denotes	developmental
T277	1265-1268	CC	denotes	and
T278	1269-1275	NN	denotes	tissue
T280	1275-1276	HYPH	denotes	-
T279	1276-1284	JJ	denotes	specific
T273	1285-1294	NNS	denotes	functions
T281	1295-1297	IN	denotes	of
T282	1298-1306	JJ	denotes	distinct
T284	1307-1310	NN	denotes	Xpd
T285	1311-1317	NN	denotes	allele
T283	1318-1326	NNS	denotes	products
T286	1326-1328	,	denotes	,
T287	1328-1331	CC	denotes	and
T288	1332-1333	-LRB-	denotes	(
T289	1333-1336	LS	denotes	iii
T291	1336-1337	-RRB-	denotes	)
T292	1338-1350	JJ	denotes	interallelic
T290	1351-1366	NN	denotes	complementation
T293	1366-1368	,	denotes	,
T294	1368-1369	DT	denotes	a
T295	1370-1380	NN	denotes	phenomenon
T296	1381-1387	RB	denotes	rarely
T297	1388-1396	VBN	denotes	reported
T298	1397-1399	IN	denotes	at
T299	1400-1410	RB	denotes	clinically
T300	1411-1419	JJ	denotes	relevant
T301	1420-1424	NNS	denotes	loci
T302	1425-1427	IN	denotes	in
T303	1428-1435	NNS	denotes	mammals
T304	1435-1436	.	denotes	.
T305	1436-1662	sentence	denotes	Our data suggest a re-evaluation of the contribution of “null” alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.
T306	1437-1440	PRP$	denotes	Our
T307	1441-1445	NNS	denotes	data
T308	1446-1453	VBP	denotes	suggest
T309	1454-1455	DT	denotes	a
T310	1456-1469	NN	denotes	re-evaluation
T311	1470-1472	IN	denotes	of
T312	1473-1476	DT	denotes	the
T313	1477-1489	NN	denotes	contribution
T314	1490-1492	IN	denotes	of
T315	1493-1494	``	denotes	“
T316	1494-1498	JJ	denotes	null
T318	1498-1499	''	denotes	”
T317	1500-1507	NNS	denotes	alleles
T319	1508-1510	IN	denotes	to
T320	1511-1514	NN	denotes	XPD
T321	1515-1524	NNS	denotes	disorders
T322	1525-1528	CC	denotes	and
T323	1529-1538	VBP	denotes	highlight
T324	1539-1542	DT	denotes	the
T325	1543-1552	NN	denotes	potential
T326	1553-1555	IN	denotes	of
T327	1556-1568	NNS	denotes	combinations
T328	1569-1571	IN	denotes	of
T329	1572-1581	JJ	denotes	recessive
T330	1582-1589	NNS	denotes	alleles
T331	1590-1592	TO	denotes	to
T332	1593-1599	VB	denotes	affect
T333	1600-1604	CC	denotes	both
T335	1605-1611	JJ	denotes	normal
T336	1612-1615	CC	denotes	and
T337	1616-1628	JJ	denotes	pathological
T338	1629-1639	JJ	denotes	phenotypic
T334	1640-1650	NN	denotes	plasticity
T339	1651-1653	IN	denotes	in
T340	1654-1661	NNS	denotes	mammals
T341	1661-1662	.	denotes	.
T565	1900-1912	JJ	denotes	Interallelic
T566	1913-1928	NN	denotes	complementation
T568	1929-1931	VBZ	denotes	is
T567	1932-1939	VBN	denotes	defined
T569	1940-1942	IN	denotes	as
T570	1943-1946	DT	denotes	the
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T573	1958-1961	CD	denotes	two
T575	1962-1976	RB	denotes	differentially
T576	1977-1984	VBN	denotes	mutated
T574	1985-1992	NNS	denotes	alleles
T577	1993-1995	TO	denotes	to
T578	1996-2004	VB	denotes	function
T579	2005-2011	RBR	denotes	better
T580	2012-2020	RB	denotes	together
T581	2021-2025	IN	denotes	than
T583	2026-2032	DT	denotes	either
T582	2033-2036	MD	denotes	can
T584	2037-2039	IN	denotes	on
T585	2040-2043	PRP$	denotes	its
T586	2044-2047	JJ	denotes	own
T587	2047-2048	.	denotes	.
T588	2048-2195	sentence	denotes	Despite its near universality in lower organisms [1], its potential to contribute to clinical heterogeneity in human disease is seldom considered.
T589	2049-2056	IN	denotes	Despite
T591	2057-2060	PRP$	denotes	its
T593	2061-2065	JJ	denotes	near
T592	2066-2078	NN	denotes	universality
T594	2079-2081	IN	denotes	in
T595	2082-2087	JJR	denotes	lower
T596	2088-2097	NNS	denotes	organisms
T597	2098-2099	-LRB-	denotes	[
T598	2099-2100	CD	denotes	1
T599	2100-2101	-RRB-	denotes	]
T600	2101-2103	,	denotes	,
T601	2103-2106	PRP$	denotes	its
T602	2107-2116	NN	denotes	potential
T603	2117-2119	TO	denotes	to
T604	2120-2130	VB	denotes	contribute
T605	2131-2133	IN	denotes	to
T606	2134-2142	JJ	denotes	clinical
T607	2143-2156	NN	denotes	heterogeneity
T608	2157-2159	IN	denotes	in
T609	2160-2165	JJ	denotes	human
T610	2166-2173	NN	denotes	disease
T611	2174-2176	VBZ	denotes	is
T612	2177-2183	RB	denotes	seldom
T590	2184-2194	VBN	denotes	considered
T613	2194-2195	.	denotes	.
T614	2195-2523	sentence	denotes	Evidence of interallelic complementation at clinically relevant loci is limited to biochemical and cell-based studies of a handful of metabolic disorders with defects in enzymes including propinyl-CoA carboxylase [2], argininosuccinate lyase [3], galactose-1-phosphate uridylyltransferase [4], and methylmalonyl CoA mutase [5].
T615	2196-2204	NN	denotes	Evidence
T617	2205-2207	IN	denotes	of
T618	2208-2220	JJ	denotes	interallelic
T619	2221-2236	NN	denotes	complementation
T620	2237-2239	IN	denotes	at
T621	2240-2250	RB	denotes	clinically
T622	2251-2259	JJ	denotes	relevant
T623	2260-2264	NNS	denotes	loci
T624	2265-2267	VBZ	denotes	is
T616	2268-2275	VBN	denotes	limited
T625	2276-2278	IN	denotes	to
T626	2279-2290	JJ	denotes	biochemical
T628	2291-2294	CC	denotes	and
T629	2295-2299	NN	denotes	cell
T631	2299-2300	HYPH	denotes	-
T630	2300-2305	VBN	denotes	based
T627	2306-2313	NNS	denotes	studies
T632	2314-2316	IN	denotes	of
T633	2317-2318	DT	denotes	a
T634	2319-2326	NN	denotes	handful
T635	2327-2329	IN	denotes	of
T636	2330-2339	JJ	denotes	metabolic
T637	2340-2349	NNS	denotes	disorders
T638	2350-2354	IN	denotes	with
T639	2355-2362	NNS	denotes	defects
T640	2363-2365	IN	denotes	in
T641	2366-2373	NNS	denotes	enzymes
T642	2374-2383	VBG	denotes	including
T643	2384-2392	NN	denotes	propinyl
T645	2392-2393	HYPH	denotes	-
T644	2393-2396	NN	denotes	CoA
T646	2397-2408	NN	denotes	carboxylase
T647	2409-2410	-LRB-	denotes	[
T648	2410-2411	CD	denotes	2
T649	2411-2412	-RRB-	denotes	]
T650	2412-2414	,	denotes	,
T651	2414-2431	NN	denotes	argininosuccinate
T652	2432-2437	NN	denotes	lyase
T653	2438-2439	-LRB-	denotes	[
T654	2439-2440	CD	denotes	3
T655	2440-2441	-RRB-	denotes	]
T656	2441-2443	,	denotes	,
T657	2443-2452	NN	denotes	galactose
T659	2452-2453	HYPH	denotes	-
T660	2453-2454	CD	denotes	1
T661	2454-2455	HYPH	denotes	-
T658	2455-2464	NN	denotes	phosphate
T662	2465-2484	NN	denotes	uridylyltransferase
T663	2485-2486	-LRB-	denotes	[
T664	2486-2487	CD	denotes	4
T665	2487-2488	-RRB-	denotes	]
T666	2488-2490	,	denotes	,
T667	2490-2493	CC	denotes	and
T668	2494-2507	NN	denotes	methylmalonyl
T670	2508-2511	NN	denotes	CoA
T669	2512-2518	NN	denotes	mutase
T671	2519-2520	-LRB-	denotes	[
T672	2520-2521	CD	denotes	5
T673	2521-2522	-RRB-	denotes	]
T674	2522-2523	.	denotes	.
T675	2523-2618	sentence	denotes	Compound heterozygotes are individuals carrying two different mutant alleles of the same gene.
T676	2524-2532	JJ	denotes	Compound
T677	2533-2546	NNS	denotes	heterozygotes
T678	2547-2550	VBP	denotes	are
T679	2551-2562	NNS	denotes	individuals
T680	2563-2571	VBG	denotes	carrying
T681	2572-2575	CD	denotes	two
T683	2576-2585	JJ	denotes	different
T684	2586-2592	JJ	denotes	mutant
T682	2593-2600	NNS	denotes	alleles
T685	2601-2603	IN	denotes	of
T686	2604-2607	DT	denotes	the
T688	2608-2612	JJ	denotes	same
T687	2613-2617	NN	denotes	gene
T689	2617-2618	.	denotes	.
T690	2618-2847	sentence	denotes	In the absence of a dominant (wild-type [wt]) allele, genetic interactions between recessive alleles (referred to here as “biallelic” effects) could result in different phenotypic outcomes including interallelic complementation.
T691	2619-2621	IN	denotes	In
T693	2622-2625	DT	denotes	the
T694	2626-2633	NN	denotes	absence
T695	2634-2636	IN	denotes	of
T696	2637-2638	DT	denotes	a
T698	2639-2647	JJ	denotes	dominant
T699	2648-2649	-LRB-	denotes	(
T700	2649-2653	JJ	denotes	wild
T702	2653-2654	HYPH	denotes	-
T701	2654-2658	NN	denotes	type
T703	2659-2660	-LRB-	denotes	[
T704	2660-2662	NN	denotes	wt
T705	2662-2663	-RRB-	denotes	]
T706	2663-2664	-RRB-	denotes	)
T697	2665-2671	NN	denotes	allele
T707	2671-2673	,	denotes	,
T708	2673-2680	JJ	denotes	genetic
T709	2681-2693	NNS	denotes	interactions
T710	2694-2701	IN	denotes	between
T711	2702-2711	JJ	denotes	recessive
T712	2712-2719	NNS	denotes	alleles
T713	2720-2721	-LRB-	denotes	(
T714	2721-2729	VBN	denotes	referred
T715	2730-2732	IN	denotes	to
T716	2733-2737	RB	denotes	here
T717	2738-2740	IN	denotes	as
T718	2741-2742	``	denotes	“
T719	2742-2751	JJ	denotes	biallelic
T721	2751-2752	''	denotes	”
T720	2753-2760	NNS	denotes	effects
T722	2760-2761	-RRB-	denotes	)
T723	2762-2767	MD	denotes	could
T692	2768-2774	VB	denotes	result
T724	2775-2777	IN	denotes	in
T725	2778-2787	JJ	denotes	different
T727	2788-2798	JJ	denotes	phenotypic
T726	2799-2807	NNS	denotes	outcomes
T728	2808-2817	VBG	denotes	including
T729	2818-2830	JJ	denotes	interallelic
T730	2831-2846	NN	denotes	complementation
T731	2846-2847	.	denotes	.
T732	2847-3183	sentence	denotes	Although amelioration of disease symptoms by interallelic complementation would create an ascertainment bias in the clinic, the lack of evidence concerning interallelic complementation or other biallelic effects in human disease is likely caused by the difficulty in distinguishing such effects from environment and genetic background.
T733	2848-2856	IN	denotes	Although
T735	2857-2869	NN	denotes	amelioration
T736	2870-2872	IN	denotes	of
T737	2873-2880	NN	denotes	disease
T738	2881-2889	NNS	denotes	symptoms
T739	2890-2892	IN	denotes	by
T740	2893-2905	JJ	denotes	interallelic
T741	2906-2921	NN	denotes	complementation
T742	2922-2927	MD	denotes	would
T734	2928-2934	VB	denotes	create
T744	2935-2937	DT	denotes	an
T746	2938-2951	NN	denotes	ascertainment
T745	2952-2956	NN	denotes	bias
T747	2957-2959	IN	denotes	in
T748	2960-2963	DT	denotes	the
T749	2964-2970	NN	denotes	clinic
T750	2970-2972	,	denotes	,
T751	2972-2975	DT	denotes	the
T752	2976-2980	NN	denotes	lack
T753	2981-2983	IN	denotes	of
T754	2984-2992	NN	denotes	evidence
T755	2993-3003	VBG	denotes	concerning
T756	3004-3016	JJ	denotes	interallelic
T757	3017-3032	NN	denotes	complementation
T758	3033-3035	CC	denotes	or
T759	3036-3041	JJ	denotes	other
T761	3042-3051	JJ	denotes	biallelic
T760	3052-3059	NNS	denotes	effects
T762	3060-3062	IN	denotes	in
T763	3063-3068	JJ	denotes	human
T764	3069-3076	NN	denotes	disease
T765	3077-3079	VBZ	denotes	is
T766	3080-3086	RB	denotes	likely
T743	3087-3093	VBN	denotes	caused
T767	3094-3096	IN	denotes	by
T768	3097-3100	DT	denotes	the
T769	3101-3111	NN	denotes	difficulty
T770	3112-3114	IN	denotes	in
T771	3115-3129	VBG	denotes	distinguishing
T772	3130-3134	JJ	denotes	such
T773	3135-3142	NNS	denotes	effects
T774	3143-3147	IN	denotes	from
T775	3148-3159	NN	denotes	environment
T776	3160-3163	CC	denotes	and
T777	3164-3171	JJ	denotes	genetic
T778	3172-3182	NN	denotes	background
T779	3182-3183	.	denotes	.
T780	3183-3484	sentence	denotes	XPD encodes one of the two helicase components of basal transcription/DNA repair factor IIH (TFIIH), a ten-subunit, multifunctional complex that is essential for multiple processes, including basal transcription initiation and DNA damage repair via the nucleotide excision repair (NER) pathway [6,7].
T781	3184-3187	NN	denotes	XPD
T782	3188-3195	VBZ	denotes	encodes
T783	3196-3199	CD	denotes	one
T784	3200-3202	IN	denotes	of
T785	3203-3206	DT	denotes	the
T787	3207-3210	CD	denotes	two
T788	3211-3219	NN	denotes	helicase
T786	3220-3230	NNS	denotes	components
T789	3231-3233	IN	denotes	of
T790	3234-3239	JJ	denotes	basal
T792	3240-3253	NN	denotes	transcription
T793	3253-3254	HYPH	denotes	/
T794	3254-3257	NN	denotes	DNA
T795	3258-3264	NN	denotes	repair
T796	3265-3271	NN	denotes	factor
T791	3272-3275	NN	denotes	IIH
T797	3276-3277	-LRB-	denotes	(
T798	3277-3282	NN	denotes	TFIIH
T799	3282-3283	-RRB-	denotes	)
T800	3283-3285	,	denotes	,
T801	3285-3286	DT	denotes	a
T803	3287-3290	CD	denotes	ten
T805	3290-3291	HYPH	denotes	-
T804	3291-3298	NN	denotes	subunit
T806	3298-3300	,	denotes	,
T807	3300-3315	JJ	denotes	multifunctional
T802	3316-3323	NN	denotes	complex
T808	3324-3328	WDT	denotes	that
T809	3329-3331	VBZ	denotes	is
T810	3332-3341	JJ	denotes	essential
T811	3342-3345	IN	denotes	for
T812	3346-3354	JJ	denotes	multiple
T813	3355-3364	NNS	denotes	processes
T814	3364-3366	,	denotes	,
T815	3366-3375	VBG	denotes	including
T816	3376-3381	JJ	denotes	basal
T818	3382-3395	NN	denotes	transcription
T817	3396-3406	NN	denotes	initiation
T819	3407-3410	CC	denotes	and
T820	3411-3414	NN	denotes	DNA
T822	3415-3421	NN	denotes	damage
T821	3422-3428	NN	denotes	repair
T823	3429-3432	IN	denotes	via
T824	3433-3436	DT	denotes	the
T826	3437-3447	NN	denotes	nucleotide
T828	3448-3456	NN	denotes	excision
T827	3457-3463	NN	denotes	repair
T829	3464-3465	-LRB-	denotes	(
T830	3465-3468	NN	denotes	NER
T831	3468-3469	-RRB-	denotes	)
T825	3470-3477	NN	denotes	pathway
T832	3478-3479	-LRB-	denotes	[
T834	3479-3480	CD	denotes	6
T835	3480-3481	,	denotes	,
T833	3481-3482	CD	denotes	7
T836	3482-3483	-RRB-	denotes	]
T837	3483-3484	.	denotes	.
T838	3484-3714	sentence	denotes	Alterations in XPD resulting in defective TFIIH function are associated with UV-sensitive, multisystem disorders including xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD) [8–10].
T839	3485-3496	NNS	denotes	Alterations
T841	3497-3499	IN	denotes	in
T842	3500-3503	NN	denotes	XPD
T843	3504-3513	VBG	denotes	resulting
T844	3514-3516	IN	denotes	in
T845	3517-3526	JJ	denotes	defective
T847	3527-3532	NN	denotes	TFIIH
T846	3533-3541	NN	denotes	function
T848	3542-3545	VBP	denotes	are
T840	3546-3556	VBN	denotes	associated
T849	3557-3561	IN	denotes	with
T850	3562-3564	NN	denotes	UV
T852	3564-3565	HYPH	denotes	-
T851	3565-3574	JJ	denotes	sensitive
T854	3574-3576	,	denotes	,
T855	3576-3587	JJ	denotes	multisystem
T853	3588-3597	NNS	denotes	disorders
T856	3598-3607	VBG	denotes	including
T857	3608-3617	NN	denotes	xeroderma
T858	3618-3629	NN	denotes	pigmentosum
T859	3630-3631	-LRB-	denotes	(
T860	3631-3633	NN	denotes	XP
T861	3633-3634	-RRB-	denotes	)
T862	3634-3636	,	denotes	,
T863	3636-3638	NN	denotes	XP
T864	3639-3647	VBN	denotes	combined
T865	3648-3652	IN	denotes	with
T866	3653-3661	NN	denotes	Cockayne
T867	3662-3670	NN	denotes	syndrome
T868	3671-3672	-LRB-	denotes	(
T869	3672-3674	NN	denotes	CS
T870	3674-3675	-RRB-	denotes	)
T871	3675-3677	,	denotes	,
T872	3677-3680	CC	denotes	and
T873	3681-3700	NN	denotes	trichothiodystrophy
T874	3701-3702	-LRB-	denotes	(
T875	3702-3705	NN	denotes	TTD
T876	3705-3706	-RRB-	denotes	)
T877	3707-3708	-LRB-	denotes	[
T878	3708-3709	CD	denotes	8
T879	3709-3710	SYM	denotes	–
T880	3710-3712	CD	denotes	10
T881	3712-3713	-RRB-	denotes	]
T882	3713-3714	.	denotes	.
T883	3714-3826	sentence	denotes	XP is marked by sun-induced pigmentation anomalies and a greater than 1,000-fold elevation in skin cancer risk.
T884	3715-3717	NN	denotes	XP
T886	3718-3720	VBZ	denotes	is
T885	3721-3727	VBN	denotes	marked
T887	3728-3730	IN	denotes	by
T888	3731-3734	NN	denotes	sun
T890	3734-3735	HYPH	denotes	-
T889	3735-3742	VBN	denotes	induced
T892	3743-3755	NN	denotes	pigmentation
T891	3756-3765	NNS	denotes	anomalies
T893	3766-3769	CC	denotes	and
T894	3770-3771	DT	denotes	a
T896	3772-3779	JJR	denotes	greater
T898	3780-3784	IN	denotes	than
T897	3785-3790	CD	denotes	1,000
T900	3790-3791	HYPH	denotes	-
T899	3791-3795	RB	denotes	fold
T895	3796-3805	NN	denotes	elevation
T901	3806-3808	IN	denotes	in
T902	3809-3813	NN	denotes	skin
T903	3814-3820	NN	denotes	cancer
T904	3821-3825	NN	denotes	risk
T905	3825-3826	.	denotes	.
T906	3826-3916	sentence	denotes	Severe cases can also present with growth retardation and primary neurodegeneration [11].
T907	3827-3833	JJ	denotes	Severe
T908	3834-3839	NNS	denotes	cases
T910	3840-3843	MD	denotes	can
T911	3844-3848	RB	denotes	also
T909	3849-3856	VB	denotes	present
T912	3857-3861	IN	denotes	with
T913	3862-3868	NN	denotes	growth
T914	3869-3880	NN	denotes	retardation
T915	3881-3884	CC	denotes	and
T916	3885-3892	JJ	denotes	primary
T917	3893-3910	NN	denotes	neurodegeneration
T918	3911-3912	-LRB-	denotes	[
T919	3912-3914	CD	denotes	11
T920	3914-3915	-RRB-	denotes	]
T921	3915-3916	.	denotes	.
T922	3916-4151	sentence	denotes	CS and TTD, on the other hand, are segmental progeroid disorders characterised by progressive post-natal growth failure and primary demyelination resulting in severe neurodysfunction, but without a clear cancer predisposition [12–15].
T923	3917-3919	NN	denotes	CS
T925	3920-3923	CC	denotes	and
T926	3924-3927	NN	denotes	TTD
T927	3927-3929	,	denotes	,
T928	3929-3931	IN	denotes	on
T929	3932-3935	DT	denotes	the
T931	3936-3941	JJ	denotes	other
T930	3942-3946	NN	denotes	hand
T932	3946-3948	,	denotes	,
T924	3948-3951	VBP	denotes	are
T933	3952-3961	JJ	denotes	segmental
T935	3962-3971	JJ	denotes	progeroid
T934	3972-3981	NNS	denotes	disorders
T936	3982-3995	VBN	denotes	characterised
T937	3996-3998	IN	denotes	by
T938	3999-4010	JJ	denotes	progressive
T940	4011-4021	JJ	denotes	post-natal
T941	4022-4028	NN	denotes	growth
T939	4029-4036	NN	denotes	failure
T942	4037-4040	CC	denotes	and
T943	4041-4048	JJ	denotes	primary
T944	4049-4062	NN	denotes	demyelination
T945	4063-4072	VBG	denotes	resulting
T946	4073-4075	IN	denotes	in
T947	4076-4082	JJ	denotes	severe
T948	4083-4099	NN	denotes	neurodysfunction
T949	4099-4101	,	denotes	,
T950	4101-4104	CC	denotes	but
T951	4105-4112	IN	denotes	without
T952	4113-4114	DT	denotes	a
T954	4115-4120	JJ	denotes	clear
T955	4121-4127	NN	denotes	cancer
T953	4128-4142	NN	denotes	predisposition
T956	4143-4144	-LRB-	denotes	[
T957	4144-4146	CD	denotes	12
T958	4146-4147	SYM	denotes	–
T959	4147-4149	CD	denotes	15
T960	4149-4150	-RRB-	denotes	]
T961	4150-4151	.	denotes	.
T962	4151-4339	sentence	denotes	Patients with TTD additionally display hallmark sulphur-deficient brittle hair and nails and scaling skin [13], resulting from a basal transcription defect in specific cell types [16,17].
T963	4152-4160	NNS	denotes	Patients
T965	4161-4165	IN	denotes	with
T966	4166-4169	NN	denotes	TTD
T967	4170-4182	RB	denotes	additionally
T964	4183-4190	VBP	denotes	display
T968	4191-4199	NN	denotes	hallmark
T970	4200-4207	NN	denotes	sulphur
T972	4207-4208	HYPH	denotes	-
T971	4208-4217	JJ	denotes	deficient
T973	4218-4225	JJ	denotes	brittle
T969	4226-4230	NN	denotes	hair
T974	4231-4234	CC	denotes	and
T975	4235-4240	NNS	denotes	nails
T976	4241-4244	CC	denotes	and
T977	4245-4252	JJ	denotes	scaling
T978	4253-4257	NN	denotes	skin
T979	4258-4259	-LRB-	denotes	[
T980	4259-4261	CD	denotes	13
T981	4261-4262	-RRB-	denotes	]
T982	4262-4264	,	denotes	,
T983	4264-4273	VBG	denotes	resulting
T984	4274-4278	IN	denotes	from
T985	4279-4280	DT	denotes	a
T987	4281-4286	JJ	denotes	basal
T988	4287-4300	NN	denotes	transcription
T986	4301-4307	NN	denotes	defect
T989	4308-4310	IN	denotes	in
T990	4311-4319	JJ	denotes	specific
T992	4320-4324	NN	denotes	cell
T991	4325-4330	NNS	denotes	types
T993	4331-4332	-LRB-	denotes	[
T995	4332-4334	CD	denotes	16
T996	4334-4335	,	denotes	,
T994	4335-4337	CD	denotes	17
T997	4337-4338	-RRB-	denotes	]
T998	4338-4339	.	denotes	.
T999	4339-4505	sentence	denotes	A related disorder with the cancer predisposition of XP combined with the neurodevelopmental complications of CS (XPCS), although rare, has also been described [18].
T1000	4340-4341	DT	denotes	A
T1002	4342-4349	JJ	denotes	related
T1001	4350-4358	NN	denotes	disorder
T1004	4359-4363	IN	denotes	with
T1005	4364-4367	DT	denotes	the
T1007	4368-4374	NN	denotes	cancer
T1006	4375-4389	NN	denotes	predisposition
T1008	4390-4392	IN	denotes	of
T1009	4393-4395	NN	denotes	XP
T1010	4396-4404	VBN	denotes	combined
T1011	4405-4409	IN	denotes	with
T1012	4410-4413	DT	denotes	the
T1014	4414-4432	JJ	denotes	neurodevelopmental
T1013	4433-4446	NNS	denotes	complications
T1015	4447-4449	IN	denotes	of
T1016	4450-4452	NN	denotes	CS
T1017	4453-4454	-LRB-	denotes	(
T1018	4454-4458	NN	denotes	XPCS
T1019	4458-4459	-RRB-	denotes	)
T1020	4459-4461	,	denotes	,
T1021	4461-4469	IN	denotes	although
T1022	4470-4474	JJ	denotes	rare
T1023	4474-4476	,	denotes	,
T1024	4476-4479	VBZ	denotes	has
T1025	4480-4484	RB	denotes	also
T1026	4485-4489	VBN	denotes	been
T1003	4490-4499	VBN	denotes	described
T1027	4500-4501	-LRB-	denotes	[
T1028	4501-4503	CD	denotes	18
T1029	4503-4504	-RRB-	denotes	]
T1030	4504-4505	.	denotes	.
T1031	4505-4687	sentence	denotes	Many XPD mutations are associated with an exclusive disease phenotype (e.g., XPDR722W with TTD and XPDR683W with XP) and are thus viewed as causative of the corresponding syndromes.
T1032	4506-4510	JJ	denotes	Many
T1034	4511-4514	NN	denotes	XPD
T1033	4515-4524	NNS	denotes	mutations
T1036	4525-4528	VBP	denotes	are
T1035	4529-4539	VBN	denotes	associated
T1037	4540-4544	IN	denotes	with
T1038	4545-4547	DT	denotes	an
T1040	4548-4557	JJ	denotes	exclusive
T1041	4558-4565	NN	denotes	disease
T1039	4566-4575	NN	denotes	phenotype
T1042	4576-4577	-LRB-	denotes	(
T1044	4577-4581	FW	denotes	e.g.
T1045	4581-4583	,	denotes	,
T1043	4583-4591	NN	denotes	XPDR722W
T1046	4592-4596	IN	denotes	with
T1047	4597-4600	NN	denotes	TTD
T1048	4601-4604	CC	denotes	and
T1049	4605-4613	NN	denotes	XPDR683W
T1050	4614-4618	IN	denotes	with
T1051	4619-4621	NN	denotes	XP
T1052	4621-4622	-RRB-	denotes	)
T1053	4623-4626	CC	denotes	and
T1054	4627-4630	VBP	denotes	are
T1056	4631-4635	RB	denotes	thus
T1055	4636-4642	VBN	denotes	viewed
T1057	4643-4645	IN	denotes	as
T1058	4646-4655	JJ	denotes	causative
T1059	4656-4658	IN	denotes	of
T1060	4659-4662	DT	denotes	the
T1062	4663-4676	VBG	denotes	corresponding
T1061	4677-4686	NNS	denotes	syndromes
T1063	4686-4687	.	denotes	.
T1064	4687-4786	sentence	denotes	Alleles not associated exclusively with one disorder are considered “likely null” alleles [19,20].
T1065	4688-4695	NNS	denotes	Alleles
T1067	4696-4699	RB	denotes	not
T1068	4700-4710	VBN	denotes	associated
T1069	4711-4722	RB	denotes	exclusively
T1070	4723-4727	IN	denotes	with
T1071	4728-4731	CD	denotes	one
T1072	4732-4740	NN	denotes	disorder
T1073	4741-4744	VBP	denotes	are
T1066	4745-4755	VBN	denotes	considered
T1074	4756-4757	``	denotes	“
T1076	4757-4763	RB	denotes	likely
T1077	4764-4768	JJ	denotes	null
T1078	4768-4769	''	denotes	”
T1075	4770-4777	NNS	denotes	alleles
T1079	4778-4779	-LRB-	denotes	[
T1081	4779-4781	CD	denotes	19
T1082	4781-4782	,	denotes	,
T1080	4782-4784	CD	denotes	20
T1083	4784-4785	-RRB-	denotes	]
T1084	4785-4786	.	denotes	.
T1085	4786-5006	sentence	denotes	Some of these alleles fail to support viability in a haploid Schizosaccharomyces pombe yeast strain with a null mutation in the XPD homologue rad15 and are thus considered devoid of significant biological activity [19].
T1086	4787-4791	DT	denotes	Some
T1088	4792-4794	IN	denotes	of
T1089	4795-4800	DT	denotes	these
T1090	4801-4808	NNS	denotes	alleles
T1087	4809-4813	VBP	denotes	fail
T1091	4814-4816	TO	denotes	to
T1092	4817-4824	VB	denotes	support
T1093	4825-4834	NN	denotes	viability
T1094	4835-4837	IN	denotes	in
T1095	4838-4839	DT	denotes	a
T1097	4840-4847	JJ	denotes	haploid
T1098	4848-4867	NNP	denotes	Schizosaccharomyces
T1099	4868-4873	NNP	denotes	pombe
T1100	4874-4879	NN	denotes	yeast
T1096	4880-4886	NN	denotes	strain
T1101	4887-4891	IN	denotes	with
T1102	4892-4893	DT	denotes	a
T1104	4894-4898	JJ	denotes	null
T1103	4899-4907	NN	denotes	mutation
T1105	4908-4910	IN	denotes	in
T1106	4911-4914	DT	denotes	the
T1108	4915-4918	NN	denotes	XPD
T1109	4919-4928	NN	denotes	homologue
T1107	4929-4934	NN	denotes	rad15
T1110	4935-4938	CC	denotes	and
T1111	4939-4942	VBP	denotes	are
T1113	4943-4947	RB	denotes	thus
T1112	4948-4958	VBN	denotes	considered
T1114	4959-4965	JJ	denotes	devoid
T1115	4966-4968	IN	denotes	of
T1116	4969-4980	JJ	denotes	significant
T1118	4981-4991	JJ	denotes	biological
T1117	4992-5000	NN	denotes	activity
T1119	5001-5002	-LRB-	denotes	[
T1120	5002-5004	CD	denotes	19
T1121	5004-5005	-RRB-	denotes	]
T1122	5005-5006	.	denotes	.
T1123	5006-5144	sentence	denotes	This classification of alleles as either causative or null currently defines what we refer to as a “monoallelic” paradigm of XPD disease.
T1124	5007-5011	DT	denotes	This
T1125	5012-5026	NN	denotes	classification
T1127	5027-5029	IN	denotes	of
T1128	5030-5037	NNS	denotes	alleles
T1129	5038-5040	IN	denotes	as
T1130	5041-5047	CC	denotes	either
T1131	5048-5057	JJ	denotes	causative
T1132	5058-5060	CC	denotes	or
T1133	5061-5065	JJ	denotes	null
T1134	5066-5075	RB	denotes	currently
T1126	5076-5083	VBZ	denotes	defines
T1135	5084-5088	WP	denotes	what
T1137	5089-5091	PRP	denotes	we
T1136	5092-5097	VBP	denotes	refer
T1138	5098-5100	IN	denotes	to
T1139	5101-5103	IN	denotes	as
T1140	5104-5105	DT	denotes	a
T1142	5106-5107	``	denotes	“
T1143	5107-5118	JJ	denotes	monoallelic
T1144	5118-5119	''	denotes	”
T1141	5120-5128	NN	denotes	paradigm
T1145	5129-5131	IN	denotes	of
T1146	5132-5135	NN	denotes	XPD
T1147	5136-5143	NN	denotes	disease
T1148	5143-5144	.	denotes	.
T1149	5144-5425	sentence	denotes	However, the identification in recent years of XP complementation group D patients with atypical disease presentation, including symptoms of both XP and TTD [8], casts doubt on the ability of such a monoallelic paradigm to explain clinical heterogeneity in compound heterozygotes.
T1150	5145-5152	RB	denotes	However
T1152	5152-5154	,	denotes	,
T1153	5154-5157	DT	denotes	the
T1154	5158-5172	NN	denotes	identification
T1155	5173-5175	IN	denotes	in
T1156	5176-5182	JJ	denotes	recent
T1157	5183-5188	NNS	denotes	years
T1158	5189-5191	IN	denotes	of
T1159	5192-5194	NN	denotes	XP
T1161	5195-5210	NN	denotes	complementation
T1162	5211-5216	NN	denotes	group
T1163	5217-5218	NN	denotes	D
T1160	5219-5227	NNS	denotes	patients
T1164	5228-5232	IN	denotes	with
T1165	5233-5241	JJ	denotes	atypical
T1167	5242-5249	NN	denotes	disease
T1166	5250-5262	NN	denotes	presentation
T1168	5262-5264	,	denotes	,
T1169	5264-5273	VBG	denotes	including
T1170	5274-5282	NNS	denotes	symptoms
T1171	5283-5285	IN	denotes	of
T1172	5286-5290	CC	denotes	both
T1173	5291-5293	NN	denotes	XP
T1174	5294-5297	CC	denotes	and
T1175	5298-5301	NN	denotes	TTD
T1176	5302-5303	-LRB-	denotes	[
T1177	5303-5304	CD	denotes	8
T1178	5304-5305	-RRB-	denotes	]
T1179	5305-5307	,	denotes	,
T1151	5307-5312	VBZ	denotes	casts
T1180	5313-5318	NN	denotes	doubt
T1181	5319-5321	IN	denotes	on
T1182	5322-5325	DT	denotes	the
T1183	5326-5333	NN	denotes	ability
T1184	5334-5336	IN	denotes	of
T1185	5337-5341	JJ	denotes	such
T1187	5342-5343	DT	denotes	a
T1188	5344-5355	JJ	denotes	monoallelic
T1186	5356-5364	NN	denotes	paradigm
T1189	5365-5367	TO	denotes	to
T1190	5368-5375	VB	denotes	explain
T1191	5376-5384	JJ	denotes	clinical
T1192	5385-5398	NN	denotes	heterogeneity
T1193	5399-5401	IN	denotes	in
T1194	5402-5410	NN	denotes	compound
T1195	5411-5424	NNS	denotes	heterozygotes
T1196	5424-5425	.	denotes	.
T1197	5425-5524	sentence	denotes	Previously, we generated a TTD mouse model (XPDR722W) that phenocopies the human syndrome [15,21].
T1198	5426-5436	RB	denotes	Previously
T1200	5436-5438	,	denotes	,
T1201	5438-5440	PRP	denotes	we
T1199	5441-5450	VBD	denotes	generated
T1202	5451-5452	DT	denotes	a
T1204	5453-5456	NN	denotes	TTD
T1205	5457-5462	NN	denotes	mouse
T1203	5463-5468	NN	denotes	model
T1206	5469-5470	-LRB-	denotes	(
T1207	5470-5478	NN	denotes	XPDR722W
T1208	5478-5479	-RRB-	denotes	)
T1209	5480-5484	WDT	denotes	that
T1210	5485-5496	VBZ	denotes	phenocopies
T1211	5497-5500	DT	denotes	the
T1213	5501-5506	JJ	denotes	human
T1212	5507-5515	NN	denotes	syndrome
T1214	5516-5517	-LRB-	denotes	[
T1216	5517-5519	CD	denotes	15
T1217	5519-5520	,	denotes	,
T1215	5520-5522	CD	denotes	21
T1218	5522-5523	-RRB-	denotes	]
T1219	5523-5524	.	denotes	.
T1220	5524-5815	sentence	denotes	Here we report the generation of additional mutant Xpd alleles that fail to support viability on their own but nevertheless ameliorate TTD-associated premature segmental ageing, cutaneous features, cellular DNA repair capacity, and UV survival when present in a compound heterozygote state.
T1221	5525-5529	RB	denotes	Here
T1223	5530-5532	PRP	denotes	we
T1222	5533-5539	VBP	denotes	report
T1224	5540-5543	DT	denotes	the
T1225	5544-5554	NN	denotes	generation
T1226	5555-5557	IN	denotes	of
T1227	5558-5568	JJ	denotes	additional
T1229	5569-5575	JJ	denotes	mutant
T1230	5576-5579	NN	denotes	Xpd
T1228	5580-5587	NNS	denotes	alleles
T1231	5588-5592	WDT	denotes	that
T1232	5593-5597	VBP	denotes	fail
T1233	5598-5600	TO	denotes	to
T1234	5601-5608	VB	denotes	support
T1235	5609-5618	NN	denotes	viability
T1236	5619-5621	IN	denotes	on
T1237	5622-5627	PRP$	denotes	their
T1238	5628-5631	NN	denotes	own
T1239	5632-5635	CC	denotes	but
T1240	5636-5648	RB	denotes	nevertheless
T1241	5649-5659	VBP	denotes	ameliorate
T1242	5660-5663	NN	denotes	TTD
T1244	5663-5664	HYPH	denotes	-
T1243	5664-5674	VBN	denotes	associated
T1246	5675-5684	JJ	denotes	premature
T1247	5685-5694	JJ	denotes	segmental
T1245	5695-5701	NN	denotes	ageing
T1248	5701-5703	,	denotes	,
T1249	5703-5712	JJ	denotes	cutaneous
T1250	5713-5721	NNS	denotes	features
T1251	5721-5723	,	denotes	,
T1252	5723-5731	JJ	denotes	cellular
T1254	5732-5735	NN	denotes	DNA
T1255	5736-5742	NN	denotes	repair
T1253	5743-5751	NN	denotes	capacity
T1256	5751-5753	,	denotes	,
T1257	5753-5756	CC	denotes	and
T1258	5757-5759	NN	denotes	UV
T1259	5760-5768	NN	denotes	survival
T1260	5769-5773	WRB	denotes	when
T1261	5774-5781	JJ	denotes	present
T1262	5782-5784	IN	denotes	in
T1263	5785-5786	DT	denotes	a
T1265	5787-5795	JJ	denotes	compound
T1266	5796-5808	NN	denotes	heterozygote
T1264	5809-5814	NN	denotes	state
T1267	5814-5815	.	denotes	.
T1400	5826-5836	NN	denotes	Generation
T1401	5837-5839	IN	denotes	of
T1402	5840-5843	NN	denotes	Xpd
T1404	5844-5852	NN	denotes	Compound
T1403	5853-5866	NNS	denotes	Heterozygotes
T1405	5866-6019	sentence	denotes	We generated an Xpd knock-in allele with a point mutation encoding a single amino acid change (XPDG602D) found in the XPCS patient XPCS2 (Figure 1A–1C).
T1406	5867-5869	PRP	denotes	We
T1407	5870-5879	VBD	denotes	generated
T1408	5880-5882	DT	denotes	an
T1410	5883-5886	NN	denotes	Xpd
T1411	5887-5892	VB	denotes	knock
T1412	5892-5893	HYPH	denotes	-
T1413	5893-5895	RP	denotes	in
T1409	5896-5902	NN	denotes	allele
T1414	5903-5907	IN	denotes	with
T1415	5908-5909	DT	denotes	a
T1417	5910-5915	NN	denotes	point
T1416	5916-5924	NN	denotes	mutation
T1418	5925-5933	VBG	denotes	encoding
T1419	5934-5935	DT	denotes	a
T1421	5936-5942	JJ	denotes	single
T1422	5943-5948	NN	denotes	amino
T1423	5949-5953	NN	denotes	acid
T1420	5954-5960	NN	denotes	change
T1424	5961-5962	-LRB-	denotes	(
T1425	5962-5970	NN	denotes	XPDG602D
T1426	5970-5971	-RRB-	denotes	)
T1427	5972-5977	VBN	denotes	found
T1428	5978-5980	IN	denotes	in
T1429	5981-5984	DT	denotes	the
T1431	5985-5989	NN	denotes	XPCS
T1430	5990-5997	NN	denotes	patient
T1432	5998-6003	NN	denotes	XPCS2
T1433	6004-6005	-LRB-	denotes	(
T1435	6005-6011	NN	denotes	Figure
T1434	6012-6014	NN	denotes	1A
T1436	6014-6015	SYM	denotes	–
T1437	6015-6017	NN	denotes	1C
T1438	6017-6018	-RRB-	denotes	)
T1439	6018-6019	.	denotes	.
T1440	6019-6311	sentence	denotes	mRNA expression from the targeted allele could be detected in embryonic stem cells by RT-PCR (Figure 1D), although expression was reduced approximately 5-fold relative to wt mRNA transcript levels as determined by Northern blotting of RNA from the testis of heterozygous animals (Figure 1E).
T1441	6020-6024	NN	denotes	mRNA
T1442	6025-6035	NN	denotes	expression
T1444	6036-6040	IN	denotes	from
T1445	6041-6044	DT	denotes	the
T1447	6045-6053	VBN	denotes	targeted
T1446	6054-6060	NN	denotes	allele
T1448	6061-6066	MD	denotes	could
T1449	6067-6069	VB	denotes	be
T1443	6070-6078	VBN	denotes	detected
T1450	6079-6081	IN	denotes	in
T1451	6082-6091	JJ	denotes	embryonic
T1453	6092-6096	NN	denotes	stem
T1452	6097-6102	NNS	denotes	cells
T1454	6103-6105	IN	denotes	by
T1455	6106-6108	NN	denotes	RT
T1457	6108-6109	HYPH	denotes	-
T1456	6109-6112	NN	denotes	PCR
T1458	6113-6114	-LRB-	denotes	(
T1460	6114-6120	NN	denotes	Figure
T1459	6121-6123	NN	denotes	1D
T1461	6123-6124	-RRB-	denotes	)
T1462	6124-6126	,	denotes	,
T1463	6126-6134	IN	denotes	although
T1465	6135-6145	NN	denotes	expression
T1466	6146-6149	VBD	denotes	was
T1464	6150-6157	VBN	denotes	reduced
T1467	6158-6171	RB	denotes	approximately
T1468	6172-6173	CD	denotes	5
T1469	6173-6174	HYPH	denotes	-
T1470	6174-6178	RB	denotes	fold
T1471	6179-6187	JJ	denotes	relative
T1472	6188-6190	IN	denotes	to
T1473	6191-6193	NN	denotes	wt
T1475	6194-6198	NN	denotes	mRNA
T1476	6199-6209	NN	denotes	transcript
T1474	6210-6216	NNS	denotes	levels
T1477	6217-6219	IN	denotes	as
T1478	6220-6230	VBN	denotes	determined
T1479	6231-6233	IN	denotes	by
T1480	6234-6242	NNP	denotes	Northern
T1481	6243-6251	VBG	denotes	blotting
T1482	6252-6254	IN	denotes	of
T1483	6255-6258	NN	denotes	RNA
T1484	6259-6263	IN	denotes	from
T1485	6264-6267	DT	denotes	the
T1486	6268-6274	NN	denotes	testis
T1487	6275-6277	IN	denotes	of
T1488	6278-6290	JJ	denotes	heterozygous
T1489	6291-6298	NNS	denotes	animals
T1490	6299-6300	-LRB-	denotes	(
T1492	6300-6306	NN	denotes	Figure
T1491	6307-6309	NN	denotes	1E
T1493	6309-6310	-RRB-	denotes	)
T1494	6310-6311	.	denotes	.
T1495	6311-6495	sentence	denotes	Because patient XPCS2 was a hemizygote with mutant XPD protein (XPDG602D) expressed from a single allele, the corresponding mutation was expected to be viable in the homozygous state.
T1496	6312-6319	IN	denotes	Because
T1498	6320-6327	NN	denotes	patient
T1499	6328-6333	NN	denotes	XPCS2
T1497	6334-6337	VBD	denotes	was
T1501	6338-6339	DT	denotes	a
T1502	6340-6350	NN	denotes	hemizygote
T1503	6351-6355	IN	denotes	with
T1504	6356-6362	JJ	denotes	mutant
T1506	6363-6366	NN	denotes	XPD
T1505	6367-6374	NN	denotes	protein
T1507	6375-6376	-LRB-	denotes	(
T1508	6376-6384	NN	denotes	XPDG602D
T1509	6384-6385	-RRB-	denotes	)
T1510	6386-6395	VBN	denotes	expressed
T1511	6396-6400	IN	denotes	from
T1512	6401-6402	DT	denotes	a
T1514	6403-6409	JJ	denotes	single
T1513	6410-6416	NN	denotes	allele
T1515	6416-6418	,	denotes	,
T1516	6418-6421	DT	denotes	the
T1518	6422-6435	VBG	denotes	corresponding
T1517	6436-6444	NN	denotes	mutation
T1519	6445-6448	VBD	denotes	was
T1500	6449-6457	VBN	denotes	expected
T1520	6458-6460	TO	denotes	to
T1521	6461-6463	VB	denotes	be
T1522	6464-6470	JJ	denotes	viable
T1523	6471-6473	IN	denotes	in
T1524	6474-6477	DT	denotes	the
T1526	6478-6488	JJ	denotes	homozygous
T1525	6489-6494	NN	denotes	state
T1527	6494-6495	.	denotes	.
T1528	6495-6632	sentence	denotes	However, homozygous mutant mice were not observed, neither amongst live births nor embryonic day 13.5 (E13.5) or E3.5 embryos (Table 1).
T1529	6496-6503	RB	denotes	However
T1531	6503-6505	,	denotes	,
T1532	6505-6515	JJ	denotes	homozygous
T1534	6516-6522	JJ	denotes	mutant
T1533	6523-6527	NNS	denotes	mice
T1535	6528-6532	VBD	denotes	were
T1536	6533-6536	RB	denotes	not
T1530	6537-6545	VBN	denotes	observed
T1537	6545-6547	,	denotes	,
T1538	6547-6554	CC	denotes	neither
T1539	6555-6562	IN	denotes	amongst
T1540	6563-6567	JJ	denotes	live
T1541	6568-6574	NNS	denotes	births
T1542	6575-6578	CC	denotes	nor
T1543	6579-6588	JJ	denotes	embryonic
T1544	6589-6592	NN	denotes	day
T1546	6593-6597	CD	denotes	13.5
T1547	6598-6599	-LRB-	denotes	(
T1548	6599-6604	NN	denotes	E13.5
T1549	6604-6605	-RRB-	denotes	)
T1550	6606-6608	CC	denotes	or
T1551	6609-6613	NN	denotes	E3.5
T1545	6614-6621	NNS	denotes	embryos
T1552	6622-6623	-LRB-	denotes	(
T1553	6623-6628	NN	denotes	Table
T1554	6629-6630	CD	denotes	1
T1555	6630-6631	-RRB-	denotes	)
T1556	6631-6632	.	denotes	.
T1557	6632-6727	sentence	denotes	The corresponding hypomorphic, mutant allele was thus designated as homozygous lethal (†XPCS).
T1558	6633-6636	DT	denotes	The
T1560	6637-6650	VBG	denotes	corresponding
T1561	6651-6662	JJ	denotes	hypomorphic
T1562	6662-6664	,	denotes	,
T1563	6664-6670	JJ	denotes	mutant
T1559	6671-6677	NN	denotes	allele
T1565	6678-6681	VBD	denotes	was
T1566	6682-6686	RB	denotes	thus
T1564	6687-6697	VBN	denotes	designated
T1567	6698-6700	IN	denotes	as
T1568	6701-6711	JJ	denotes	homozygous
T1569	6712-6718	JJ	denotes	lethal
T1570	6719-6720	-LRB-	denotes	(
T1571	6720-6725	NN	denotes	†XPCS
T1572	6725-6726	-RRB-	denotes	)
T1573	6726-6727	.	denotes	.
T1574	6727-6917	sentence	denotes	Homozygous lethality of the XPCS allele is likely due to reduced levels of expression of this essential protein as a result of gene targeting (Figure 1A) rather than to the mutation itself.
T1575	6728-6738	JJ	denotes	Homozygous
T1576	6739-6748	NN	denotes	lethality
T1578	6749-6751	IN	denotes	of
T1579	6752-6755	DT	denotes	the
T1581	6756-6760	NN	denotes	XPCS
T1580	6761-6767	NN	denotes	allele
T1577	6768-6770	VBZ	denotes	is
T1582	6771-6777	RB	denotes	likely
T1583	6778-6781	IN	denotes	due
T1584	6782-6784	IN	denotes	to
T1585	6785-6792	VBN	denotes	reduced
T1586	6793-6799	NNS	denotes	levels
T1587	6800-6802	IN	denotes	of
T1588	6803-6813	NN	denotes	expression
T1589	6814-6816	IN	denotes	of
T1590	6817-6821	DT	denotes	this
T1592	6822-6831	JJ	denotes	essential
T1591	6832-6839	NN	denotes	protein
T1593	6840-6842	IN	denotes	as
T1594	6843-6844	DT	denotes	a
T1595	6845-6851	NN	denotes	result
T1596	6852-6854	IN	denotes	of
T1597	6855-6859	NN	denotes	gene
T1598	6860-6869	NN	denotes	targeting
T1599	6870-6871	-LRB-	denotes	(
T1601	6871-6877	NN	denotes	Figure
T1600	6878-6880	NN	denotes	1A
T1602	6880-6881	-RRB-	denotes	)
T1603	6882-6888	JJ	denotes	rather
T1604	6889-6893	IN	denotes	than
T1605	6894-6896	IN	denotes	to
T1606	6897-6900	DT	denotes	the
T1607	6901-6909	NN	denotes	mutation
T1608	6910-6916	PRP	denotes	itself
T1609	6916-6917	.	denotes	.
T1610	6917-7029	sentence	denotes	Xpd ablation (XpdKO /KO ) is similarly incompatible with life beyond the earliest stages of embryogenesis [22].
T1611	6918-6921	NN	denotes	Xpd
T1612	6922-6930	NN	denotes	ablation
T1614	6931-6932	-LRB-	denotes	(
T1616	6932-6937	NN	denotes	XpdKO
T1617	6938-6939	HYPH	denotes	/
T1615	6939-6941	NN	denotes	KO
T1618	6942-6943	-RRB-	denotes	)
T1613	6944-6946	VBZ	denotes	is
T1619	6947-6956	RB	denotes	similarly
T1620	6957-6969	JJ	denotes	incompatible
T1621	6970-6974	IN	denotes	with
T1622	6975-6979	NN	denotes	life
T1623	6980-6986	IN	denotes	beyond
T1624	6987-6990	DT	denotes	the
T1626	6991-6999	JJS	denotes	earliest
T1625	7000-7006	NNS	denotes	stages
T1627	7007-7009	IN	denotes	of
T1628	7010-7023	NN	denotes	embryogenesis
T1629	7024-7025	-LRB-	denotes	[
T1630	7025-7027	CD	denotes	22
T1631	7027-7028	-RRB-	denotes	]
T1632	7028-7029	.	denotes	.
T1633	7029-7316	sentence	denotes	Consistent with this interpretation, a different targeted Xpd mutation encoding XPDR683W, which is associated with XP in the homozygous state in humans, was similarly underexpressed and lethal in the homozygous state (designated as †XP allele) (Figure 1A–1C; Table 1; unpublished data).
T1634	7030-7040	JJ	denotes	Consistent
T1636	7041-7045	IN	denotes	with
T1637	7046-7050	DT	denotes	this
T1638	7051-7065	NN	denotes	interpretation
T1639	7065-7067	,	denotes	,
T1640	7067-7068	DT	denotes	a
T1642	7069-7078	JJ	denotes	different
T1643	7079-7087	VBN	denotes	targeted
T1644	7088-7091	NN	denotes	Xpd
T1641	7092-7100	NN	denotes	mutation
T1645	7101-7109	VBG	denotes	encoding
T1646	7110-7118	NN	denotes	XPDR683W
T1647	7118-7120	,	denotes	,
T1648	7120-7125	WDT	denotes	which
T1650	7126-7128	VBZ	denotes	is
T1649	7129-7139	VBN	denotes	associated
T1651	7140-7144	IN	denotes	with
T1652	7145-7147	NN	denotes	XP
T1653	7148-7150	IN	denotes	in
T1654	7151-7154	DT	denotes	the
T1656	7155-7165	JJ	denotes	homozygous
T1655	7166-7171	NN	denotes	state
T1657	7172-7174	IN	denotes	in
T1658	7175-7181	NNS	denotes	humans
T1659	7181-7183	,	denotes	,
T1635	7183-7186	VBD	denotes	was
T1660	7187-7196	RB	denotes	similarly
T1661	7197-7211	JJ	denotes	underexpressed
T1662	7212-7215	CC	denotes	and
T1663	7216-7222	JJ	denotes	lethal
T1664	7223-7225	IN	denotes	in
T1665	7226-7229	DT	denotes	the
T1667	7230-7240	JJ	denotes	homozygous
T1666	7241-7246	NN	denotes	state
T1668	7247-7248	-LRB-	denotes	(
T1669	7248-7258	VBN	denotes	designated
T1670	7259-7261	IN	denotes	as
T1671	7262-7265	NN	denotes	†XP
T1672	7266-7272	NN	denotes	allele
T1673	7272-7273	-RRB-	denotes	)
T1674	7274-7275	-LRB-	denotes	(
T1676	7275-7281	NN	denotes	Figure
T1675	7282-7284	NN	denotes	1A
T1677	7284-7285	SYM	denotes	–
T1678	7285-7287	NN	denotes	1C
T1679	7287-7288	:	denotes	;
T1680	7289-7294	NN	denotes	Table
T1681	7295-7296	CD	denotes	1
T1682	7296-7297	:	denotes	;
T1683	7298-7309	JJ	denotes	unpublished
T1684	7310-7314	NNS	denotes	data
T1685	7314-7315	-RRB-	denotes	)
T1686	7315-7316	.	denotes	.
T1687	7316-7535	sentence	denotes	Also, a different targeting approach leading to the use of the native 3′UTR and removal of the neo gene resulted in normalisation of XpdXPCS mRNA levels and viable homozygous XpdXPCS/XPCS (XPDG602D/G602D) animals [23].
T1688	7317-7321	RB	denotes	Also
T1690	7321-7323	,	denotes	,
T1691	7323-7324	DT	denotes	a
T1693	7325-7334	JJ	denotes	different
T1694	7335-7344	NN	denotes	targeting
T1692	7345-7353	NN	denotes	approach
T1695	7354-7361	VBG	denotes	leading
T1696	7362-7364	IN	denotes	to
T1697	7365-7368	DT	denotes	the
T1698	7369-7372	NN	denotes	use
T1699	7373-7375	IN	denotes	of
T1700	7376-7379	DT	denotes	the
T1702	7380-7386	JJ	denotes	native
T1703	7387-7388	CD	denotes	3
T1704	7388-7389	SYM	denotes	′
T1701	7389-7392	NN	denotes	UTR
T1705	7393-7396	CC	denotes	and
T1706	7397-7404	NN	denotes	removal
T1707	7405-7407	IN	denotes	of
T1708	7408-7411	DT	denotes	the
T1710	7412-7415	NN	denotes	neo
T1709	7416-7420	NN	denotes	gene
T1689	7421-7429	VBD	denotes	resulted
T1711	7430-7432	IN	denotes	in
T1712	7433-7446	NN	denotes	normalisation
T1713	7447-7449	IN	denotes	of
T1714	7450-7457	NN	denotes	XpdXPCS
T1716	7458-7462	NN	denotes	mRNA
T1715	7463-7469	NNS	denotes	levels
T1717	7470-7473	CC	denotes	and
T1718	7474-7480	JJ	denotes	viable
T1720	7481-7491	JJ	denotes	homozygous
T1721	7492-7499	NN	denotes	XpdXPCS
T1723	7499-7500	HYPH	denotes	/
T1722	7500-7504	NN	denotes	XPCS
T1724	7505-7506	-LRB-	denotes	(
T1726	7506-7514	NN	denotes	XPDG602D
T1727	7514-7515	HYPH	denotes	/
T1725	7515-7520	NN	denotes	G602D
T1728	7520-7521	-RRB-	denotes	)
T1719	7522-7529	NNS	denotes	animals
T1729	7530-7531	-LRB-	denotes	[
T1730	7531-7533	CD	denotes	23
T1731	7533-7534	-RRB-	denotes	]
T1732	7534-7535	.	denotes	.
T7095	7546-7555	NN	denotes	Targeting
T7096	7556-7558	IN	denotes	of
T7097	7559-7562	DT	denotes	the
T7099	7563-7568	NN	denotes	Mouse
T7100	7569-7572	NN	denotes	Xpd
T7098	7573-7577	NN	denotes	Gene
T7101	7577-7698	sentence	denotes	(A) Schematic representation of the genomic structure and partial restriction map of the wt and targeted mouse Xpd loci.
T7102	7578-7579	-LRB-	denotes	(
T7103	7579-7580	LS	denotes	A
T7105	7580-7581	-RRB-	denotes	)
T7106	7582-7591	JJ	denotes	Schematic
T7104	7592-7606	NN	denotes	representation
T7107	7607-7609	IN	denotes	of
T7108	7610-7613	DT	denotes	the
T7110	7614-7621	JJ	denotes	genomic
T7109	7622-7631	NN	denotes	structure
T7111	7632-7635	CC	denotes	and
T7112	7636-7643	JJ	denotes	partial
T7114	7644-7655	NN	denotes	restriction
T7113	7656-7659	NN	denotes	map
T7115	7660-7662	IN	denotes	of
T7116	7663-7666	DT	denotes	the
T7118	7667-7669	NN	denotes	wt
T7119	7670-7673	CC	denotes	and
T7120	7674-7682	VBN	denotes	targeted
T7121	7683-7688	NN	denotes	mouse
T7122	7689-7692	NN	denotes	Xpd
T7117	7693-7697	NNS	denotes	loci
T7123	7697-7698	.	denotes	.
T7124	7698-7823	sentence	denotes	For the wt Xpd allele, shaded boxes represent coding regions of exons 12 and 19–23; the 3′UTR is represented by an open box.
T7125	7699-7702	IN	denotes	For
T7127	7703-7706	DT	denotes	the
T7129	7707-7709	NN	denotes	wt
T7130	7710-7713	NN	denotes	Xpd
T7128	7714-7720	NN	denotes	allele
T7131	7720-7722	,	denotes	,
T7132	7722-7728	JJ	denotes	shaded
T7133	7729-7734	NNS	denotes	boxes
T7134	7735-7744	VBP	denotes	represent
T7135	7745-7751	VBG	denotes	coding
T7136	7752-7759	NNS	denotes	regions
T7137	7760-7762	IN	denotes	of
T7138	7763-7768	NNS	denotes	exons
T7139	7769-7771	CD	denotes	12
T7140	7772-7775	CC	denotes	and
T7141	7776-7778	CD	denotes	19
T7142	7778-7779	SYM	denotes	–
T7143	7779-7781	CD	denotes	23
T7144	7781-7782	:	denotes	;
T7145	7783-7786	DT	denotes	the
T7147	7787-7788	CD	denotes	3
T7148	7788-7789	SYM	denotes	′
T7146	7789-7792	NN	denotes	UTR
T7149	7793-7795	VBZ	denotes	is
T7126	7796-7807	VBN	denotes	represented
T7150	7808-7810	IN	denotes	by
T7151	7811-7813	DT	denotes	an
T7153	7814-7818	JJ	denotes	open
T7152	7819-7822	NN	denotes	box
T7154	7822-7823	.	denotes	.
T7155	7823-7911	sentence	denotes	TGA indicates the translational stop codon; PolyA indicates the polyadenylation signal.
T7156	7824-7827	NN	denotes	TGA
T7157	7828-7837	VBZ	denotes	indicates
T7159	7838-7841	DT	denotes	the
T7161	7842-7855	JJ	denotes	translational
T7162	7856-7860	NN	denotes	stop
T7160	7861-7866	NN	denotes	codon
T7163	7866-7867	:	denotes	;
T7164	7868-7873	NN	denotes	PolyA
T7158	7874-7883	VBZ	denotes	indicates
T7165	7884-7887	DT	denotes	the
T7167	7888-7903	NN	denotes	polyadenylation
T7166	7904-7910	NN	denotes	signal
T7168	7910-7911	.	denotes	.
T7169	7911-8103	sentence	denotes	For the XpdTTD targeted allele, the 194–base pair (bp) human XPD cDNA fragment fused to exon 22 is indicated as a striped box including the TTD (R722W) mutation indicated by a vertical arrow.
T7170	7912-7915	IN	denotes	For
T7172	7916-7919	DT	denotes	the
T7174	7920-7926	NN	denotes	XpdTTD
T7175	7927-7935	VBN	denotes	targeted
T7173	7936-7942	NN	denotes	allele
T7176	7942-7944	,	denotes	,
T7177	7944-7947	DT	denotes	the
T7179	7948-7951	CD	denotes	194
T7181	7951-7952	HYPH	denotes	–
T7182	7952-7956	NN	denotes	base
T7180	7957-7961	NN	denotes	pair
T7183	7962-7963	-LRB-	denotes	(
T7184	7963-7965	NN	denotes	bp
T7185	7965-7966	-RRB-	denotes	)
T7186	7967-7972	JJ	denotes	human
T7187	7973-7976	NN	denotes	XPD
T7188	7977-7981	NN	denotes	cDNA
T7178	7982-7990	NN	denotes	fragment
T7189	7991-7996	VBN	denotes	fused
T7190	7997-7999	IN	denotes	to
T7191	8000-8004	NN	denotes	exon
T7192	8005-8007	CD	denotes	22
T7193	8008-8010	VBZ	denotes	is
T7171	8011-8020	VBN	denotes	indicated
T7194	8021-8023	IN	denotes	as
T7195	8024-8025	DT	denotes	a
T7197	8026-8033	VBN	denotes	striped
T7196	8034-8037	NN	denotes	box
T7198	8038-8047	VBG	denotes	including
T7199	8048-8051	DT	denotes	the
T7201	8052-8055	NN	denotes	TTD
T7202	8056-8057	-LRB-	denotes	(
T7203	8057-8062	NN	denotes	R722W
T7204	8062-8063	-RRB-	denotes	)
T7200	8064-8072	NN	denotes	mutation
T7205	8073-8082	VBN	denotes	indicated
T7206	8083-8085	IN	denotes	by
T7207	8086-8087	DT	denotes	a
T7209	8088-8096	JJ	denotes	vertical
T7208	8097-8102	NN	denotes	arrow
T7210	8102-8103	.	denotes	.
T7211	8103-8275	sentence	denotes	Chicken β-globin exons 2 and 3 including the 3′UTR are indicated as black boxes with corresponding Roman numerals followed by the β-globin polyadenylation signal (PolyA*).
T7212	8104-8111	NN	denotes	Chicken
T7214	8112-8113	NN	denotes	β
T7216	8113-8114	HYPH	denotes	-
T7215	8114-8120	NN	denotes	globin
T7217	8121-8126	NNS	denotes	exons
T7213	8127-8128	CD	denotes	2
T7219	8129-8132	CC	denotes	and
T7220	8133-8134	CD	denotes	3
T7221	8135-8144	VBG	denotes	including
T7222	8145-8148	DT	denotes	the
T7224	8149-8150	CD	denotes	3
T7225	8150-8151	HYPH	denotes	′
T7223	8151-8154	NN	denotes	UTR
T7226	8155-8158	VBP	denotes	are
T7218	8159-8168	VBN	denotes	indicated
T7227	8169-8171	IN	denotes	as
T7228	8172-8177	JJ	denotes	black
T7229	8178-8183	NNS	denotes	boxes
T7230	8184-8188	IN	denotes	with
T7231	8189-8202	VBG	denotes	corresponding
T7233	8203-8208	NNP	denotes	Roman
T7232	8209-8217	NNS	denotes	numerals
T7234	8218-8226	VBN	denotes	followed
T7235	8227-8229	IN	denotes	by
T7236	8230-8233	DT	denotes	the
T7238	8234-8235	NN	denotes	β
T7240	8235-8236	HYPH	denotes	-
T7239	8236-8242	NN	denotes	globin
T7241	8243-8258	NN	denotes	polyadenylation
T7237	8259-8265	NN	denotes	signal
T7242	8266-8267	-LRB-	denotes	(
T7243	8267-8273	NN	denotes	PolyA*
T7244	8273-8274	-RRB-	denotes	)
T7245	8274-8275	.	denotes	.
T7246	8275-8436	sentence	denotes	For the Xpd†XP and Xpd†XPCS targeted alleles, vertical arrows indicate XPCS (G602D-encoding) and XP (R683W-encoding) mutations in exons 19 and 22, respectively.
T7247	8276-8279	IN	denotes	For
T7249	8280-8283	DT	denotes	the
T7251	8284-8290	NN	denotes	Xpd†XP
T7252	8291-8294	CC	denotes	and
T7253	8295-8303	NN	denotes	Xpd†XPCS
T7254	8304-8312	VBN	denotes	targeted
T7250	8313-8320	NNS	denotes	alleles
T7255	8320-8322	,	denotes	,
T7256	8322-8330	JJ	denotes	vertical
T7257	8331-8337	NNS	denotes	arrows
T7248	8338-8346	VBP	denotes	indicate
T7258	8347-8351	NN	denotes	XPCS
T7260	8352-8353	-LRB-	denotes	(
T7262	8353-8358	NN	denotes	G602D
T7263	8358-8359	HYPH	denotes	-
T7261	8359-8367	VBG	denotes	encoding
T7264	8367-8368	-RRB-	denotes	)
T7265	8369-8372	CC	denotes	and
T7266	8373-8375	NN	denotes	XP
T7267	8376-8377	-LRB-	denotes	(
T7269	8377-8382	NN	denotes	R683W
T7270	8382-8383	HYPH	denotes	-
T7268	8383-8391	VBG	denotes	encoding
T7271	8391-8392	-RRB-	denotes	)
T7259	8393-8402	NNS	denotes	mutations
T7272	8403-8405	IN	denotes	in
T7273	8406-8411	NNS	denotes	exons
T7274	8412-8414	CD	denotes	19
T7275	8415-8418	CC	denotes	and
T7276	8419-8421	CD	denotes	22
T7277	8421-8423	,	denotes	,
T7278	8423-8435	RB	denotes	respectively
T7279	8435-8436	.	denotes	.
T7280	8436-8529	sentence	denotes	The unique 3′ probe located outside the targeting construct is marked by a thick black line.
T7281	8437-8440	DT	denotes	The
T7283	8441-8447	JJ	denotes	unique
T7284	8448-8449	CD	denotes	3
T7285	8449-8450	SYM	denotes	′
T7282	8451-8456	NN	denotes	probe
T7287	8457-8464	VBN	denotes	located
T7288	8465-8472	IN	denotes	outside
T7289	8473-8476	DT	denotes	the
T7291	8477-8486	VBG	denotes	targeting
T7290	8487-8496	NN	denotes	construct
T7292	8497-8499	VBZ	denotes	is
T7286	8500-8506	VBN	denotes	marked
T7293	8507-8509	IN	denotes	by
T7294	8510-8511	DT	denotes	a
T7296	8512-8517	JJ	denotes	thick
T7297	8518-8523	JJ	denotes	black
T7295	8524-8528	NN	denotes	line
T7298	8528-8529	.	denotes	.
T7299	8529-8609	sentence	denotes	Restriction sites: B, BamHI; C, ClaI; E, EcoRI; H, HindIII; Hp, HpaI; Sf, SfiI.
T7300	8530-8541	NN	denotes	Restriction
T7301	8542-8547	NNS	denotes	sites
T7302	8547-8549	:	denotes	:
T7303	8549-8550	NN	denotes	B
T7304	8550-8552	,	denotes	,
T7305	8552-8557	NN	denotes	BamHI
T7306	8557-8558	:	denotes	;
T7307	8559-8560	NN	denotes	C
T7308	8560-8562	,	denotes	,
T7309	8562-8566	NN	denotes	ClaI
T7310	8566-8567	:	denotes	;
T7311	8568-8569	NN	denotes	E
T7312	8569-8571	,	denotes	,
T7313	8571-8576	NN	denotes	EcoRI
T7314	8576-8577	:	denotes	;
T7315	8578-8579	NN	denotes	H
T7316	8579-8581	,	denotes	,
T7317	8581-8588	NN	denotes	HindIII
T7318	8588-8589	:	denotes	;
T7319	8590-8592	NN	denotes	Hp
T7320	8592-8594	,	denotes	,
T7321	8594-8598	NN	denotes	HpaI
T7322	8598-8599	:	denotes	;
T7323	8600-8602	NN	denotes	Sf
T7324	8602-8604	,	denotes	,
T7325	8604-8608	NN	denotes	SfiI
T7326	8608-8609	.	denotes	.
T7327	8609-8787	sentence	denotes	(B) Southern blot analysis of EcoRI-digested genomic DNA from wt, Xpd†XPCS/wt, and Xpd†XP/wt recombinant embryonic stem cell clones hybridised with the 3′ probe depicted in (A).
T7328	8610-8611	-LRB-	denotes	(
T7329	8611-8612	LS	denotes	B
T7331	8612-8613	-RRB-	denotes	)
T7332	8614-8622	NNP	denotes	Southern
T7333	8623-8627	NN	denotes	blot
T7330	8628-8636	NN	denotes	analysis
T7334	8637-8639	IN	denotes	of
T7335	8640-8645	NN	denotes	EcoRI
T7337	8645-8646	HYPH	denotes	-
T7336	8646-8654	VBN	denotes	digested
T7339	8655-8662	JJ	denotes	genomic
T7338	8663-8666	NN	denotes	DNA
T7340	8667-8671	IN	denotes	from
T7341	8672-8674	NN	denotes	wt
T7343	8674-8676	,	denotes	,
T7344	8676-8684	NN	denotes	Xpd†XPCS
T7346	8684-8685	HYPH	denotes	/
T7345	8685-8687	NN	denotes	wt
T7347	8687-8689	,	denotes	,
T7348	8689-8692	CC	denotes	and
T7349	8693-8699	NN	denotes	Xpd†XP
T7351	8699-8700	HYPH	denotes	/
T7350	8700-8702	NN	denotes	wt
T7352	8703-8714	JJ	denotes	recombinant
T7353	8715-8724	JJ	denotes	embryonic
T7355	8725-8729	NN	denotes	stem
T7354	8730-8734	NN	denotes	cell
T7342	8735-8741	NNS	denotes	clones
T7356	8742-8752	VBN	denotes	hybridised
T7357	8753-8757	IN	denotes	with
T7358	8758-8761	DT	denotes	the
T7360	8762-8763	CD	denotes	3
T7361	8763-8764	SYM	denotes	′
T7359	8765-8770	NN	denotes	probe
T7362	8771-8779	VBN	denotes	depicted
T7363	8780-8782	IN	denotes	in
T7364	8783-8784	-LRB-	denotes	(
T7365	8784-8785	NN	denotes	A
T7366	8785-8786	-RRB-	denotes	)
T7367	8786-8787	.	denotes	.
T7368	8787-8913	sentence	denotes	The wt allele yields a 6.5-kilobase (kb) fragment, whereas both targeted Xpd†XP and Xpd†XPCS alleles yield a 5.1-kb fragment.
T7369	8788-8791	DT	denotes	The
T7371	8792-8794	NN	denotes	wt
T7370	8795-8801	NN	denotes	allele
T7372	8802-8808	VBZ	denotes	yields
T7373	8809-8810	DT	denotes	a
T7375	8811-8814	CD	denotes	6.5
T7377	8814-8815	HYPH	denotes	-
T7376	8815-8823	NN	denotes	kilobase
T7378	8824-8825	-LRB-	denotes	(
T7379	8825-8827	NN	denotes	kb
T7380	8827-8828	-RRB-	denotes	)
T7374	8829-8837	NN	denotes	fragment
T7381	8837-8839	,	denotes	,
T7382	8839-8846	IN	denotes	whereas
T7384	8847-8851	CC	denotes	both
T7386	8852-8860	VBN	denotes	targeted
T7387	8861-8867	NN	denotes	Xpd†XP
T7388	8868-8871	CC	denotes	and
T7389	8872-8880	NN	denotes	Xpd†XPCS
T7385	8881-8888	NNS	denotes	alleles
T7383	8889-8894	VBP	denotes	yield
T7390	8895-8896	DT	denotes	a
T7392	8897-8900	CD	denotes	5.1
T7394	8900-8901	HYPH	denotes	-
T7393	8901-8903	NN	denotes	kb
T7391	8904-8912	NN	denotes	fragment
T7395	8912-8913	.	denotes	.
T7396	8913-9064	sentence	denotes	(C) Genotyping of wt and targeted alleles by PCR using primers F2, R1, and mR as indicated in (A) yields fragments of 399 bp and 468 bp, respectively.
T7397	8914-8915	-LRB-	denotes	(
T7398	8915-8916	LS	denotes	C
T7400	8916-8917	-RRB-	denotes	)
T7399	8918-8928	NN	denotes	Genotyping
T7401	8929-8931	IN	denotes	of
T7402	8932-8934	NN	denotes	wt
T7404	8935-8938	CC	denotes	and
T7405	8939-8947	VBN	denotes	targeted
T7403	8948-8955	NNS	denotes	alleles
T7406	8956-8958	IN	denotes	by
T7407	8959-8962	NN	denotes	PCR
T7408	8963-8968	VBG	denotes	using
T7409	8969-8976	NNS	denotes	primers
T7410	8977-8979	NN	denotes	F2
T7411	8979-8981	,	denotes	,
T7412	8981-8983	NN	denotes	R1
T7413	8983-8985	,	denotes	,
T7414	8985-8988	CC	denotes	and
T7415	8989-8991	NN	denotes	mR
T7416	8992-8994	IN	denotes	as
T7417	8995-9004	VBN	denotes	indicated
T7418	9005-9007	IN	denotes	in
T7419	9008-9009	-LRB-	denotes	(
T7420	9009-9010	LS	denotes	A
T7422	9010-9011	-RRB-	denotes	)
T7423	9012-9018	VBZ	denotes	yields
T7421	9019-9028	NNS	denotes	fragments
T7424	9029-9031	IN	denotes	of
T7425	9032-9035	CD	denotes	399
T7426	9036-9038	NN	denotes	bp
T7427	9039-9042	CC	denotes	and
T7428	9043-9046	CD	denotes	468
T7429	9047-9049	NN	denotes	bp
T7430	9049-9051	,	denotes	,
T7431	9051-9063	RB	denotes	respectively
T7432	9063-9064	.	denotes	.
T7433	9064-9308	sentence	denotes	(D) RT-PCR detection of mRNA expression originating from the targeted †XP and †XPCS alleles in embryonic stem cell clones using primers F1 (hybridising outside the targeting construct) and mR as indicated in (A) results in a 1,416-bp fragment.
T7434	9065-9066	-LRB-	denotes	(
T7435	9066-9067	LS	denotes	D
T7437	9067-9068	-RRB-	denotes	)
T7438	9069-9071	NN	denotes	RT
T7440	9071-9072	HYPH	denotes	-
T7439	9072-9075	NN	denotes	PCR
T7441	9076-9085	NN	denotes	detection
T7442	9086-9088	IN	denotes	of
T7443	9089-9093	NN	denotes	mRNA
T7444	9094-9104	NN	denotes	expression
T7445	9105-9116	VBG	denotes	originating
T7446	9117-9121	IN	denotes	from
T7447	9122-9125	DT	denotes	the
T7449	9126-9134	VBN	denotes	targeted
T7450	9135-9138	NN	denotes	†XP
T7451	9139-9142	CC	denotes	and
T7452	9143-9148	NN	denotes	†XPCS
T7448	9149-9156	NNS	denotes	alleles
T7453	9157-9159	IN	denotes	in
T7454	9160-9169	JJ	denotes	embryonic
T7456	9170-9174	NN	denotes	stem
T7455	9175-9179	NN	denotes	cell
T7457	9180-9186	NNS	denotes	clones
T7458	9187-9192	VBG	denotes	using
T7459	9193-9200	NNS	denotes	primers
T7460	9201-9203	NN	denotes	F1
T7461	9204-9205	-LRB-	denotes	(
T7462	9205-9216	VBG	denotes	hybridising
T7463	9217-9224	IN	denotes	outside
T7464	9225-9228	DT	denotes	the
T7466	9229-9238	VBG	denotes	targeting
T7465	9239-9248	NN	denotes	construct
T7467	9248-9249	-RRB-	denotes	)
T7468	9250-9253	CC	denotes	and
T7469	9254-9256	NN	denotes	mR
T7470	9257-9259	IN	denotes	as
T7471	9260-9269	VBN	denotes	indicated
T7472	9270-9272	IN	denotes	in
T7473	9273-9274	-LRB-	denotes	(
T7474	9274-9275	NN	denotes	A
T7475	9275-9276	-RRB-	denotes	)
T7436	9277-9284	VBZ	denotes	results
T7476	9285-9287	IN	denotes	in
T7477	9288-9289	DT	denotes	a
T7479	9290-9295	CD	denotes	1,416
T7481	9295-9296	HYPH	denotes	-
T7480	9296-9298	NN	denotes	bp
T7478	9299-9307	NN	denotes	fragment
T7482	9307-9308	.	denotes	.
T7483	9308-9500	sentence	denotes	(E) Northern blot analysis of total RNA isolated from testis of homozygous wt and XpdTTD/TTD, heterozygous Xpd†XPCS/wt and XpdTTD/wt, and compound heterozygous Xpd†XPCS/TTD mice as indicated.
T7484	9309-9310	-LRB-	denotes	(
T7485	9310-9311	LS	denotes	E
T7487	9311-9312	-RRB-	denotes	)
T7488	9313-9321	NNP	denotes	Northern
T7489	9322-9326	NN	denotes	blot
T7486	9327-9335	NN	denotes	analysis
T7490	9336-9338	IN	denotes	of
T7491	9339-9344	JJ	denotes	total
T7492	9345-9348	NN	denotes	RNA
T7493	9349-9357	VBN	denotes	isolated
T7494	9358-9362	IN	denotes	from
T7495	9363-9369	NN	denotes	testis
T7496	9370-9372	IN	denotes	of
T7497	9373-9383	JJ	denotes	homozygous
T7498	9384-9386	NN	denotes	wt
T7500	9387-9390	CC	denotes	and
T7501	9391-9397	NN	denotes	XpdTTD
T7503	9397-9398	HYPH	denotes	/
T7502	9398-9401	NN	denotes	TTD
T7504	9401-9403	,	denotes	,
T7505	9403-9415	JJ	denotes	heterozygous
T7507	9416-9424	NN	denotes	Xpd†XPCS
T7508	9424-9425	HYPH	denotes	/
T7506	9425-9427	NN	denotes	wt
T7509	9428-9431	CC	denotes	and
T7510	9432-9438	NN	denotes	XpdTTD
T7512	9438-9439	HYPH	denotes	/
T7511	9439-9441	NN	denotes	wt
T7513	9441-9443	,	denotes	,
T7514	9443-9446	CC	denotes	and
T7515	9447-9455	JJ	denotes	compound
T7517	9456-9468	JJ	denotes	heterozygous
T7518	9469-9477	NN	denotes	Xpd†XPCS
T7519	9477-9478	HYPH	denotes	/
T7516	9478-9481	NN	denotes	TTD
T7499	9482-9486	NNS	denotes	mice
T7520	9487-9489	IN	denotes	as
T7521	9490-9499	VBN	denotes	indicated
T7522	9499-9500	.	denotes	.
T7523	9500-9638	sentence	denotes	Hybridisation with a 1.4-kb mouse Xpd cDNA probe detects mRNAs of 4, 3.3, and 2.7 kb from wt, Xpd†XPCS, and XpdTTD alleles, respectively.
T7524	9501-9514	NN	denotes	Hybridisation
T7526	9515-9519	IN	denotes	with
T7527	9520-9521	DT	denotes	a
T7529	9522-9525	CD	denotes	1.4
T7531	9525-9526	HYPH	denotes	-
T7530	9526-9528	NN	denotes	kb
T7532	9529-9534	NN	denotes	mouse
T7533	9535-9538	NN	denotes	Xpd
T7534	9539-9543	NN	denotes	cDNA
T7528	9544-9549	NN	denotes	probe
T7525	9550-9557	VBZ	denotes	detects
T7535	9558-9563	NNS	denotes	mRNAs
T7536	9564-9566	IN	denotes	of
T7537	9567-9568	CD	denotes	4
T7539	9568-9570	,	denotes	,
T7540	9570-9573	CD	denotes	3.3
T7541	9573-9575	,	denotes	,
T7542	9575-9578	CC	denotes	and
T7543	9579-9582	CD	denotes	2.7
T7538	9583-9585	NN	denotes	kb
T7544	9586-9590	IN	denotes	from
T7545	9591-9593	NN	denotes	wt
T7547	9593-9595	,	denotes	,
T7548	9595-9603	NN	denotes	Xpd†XPCS
T7549	9603-9605	,	denotes	,
T7550	9605-9608	CC	denotes	and
T7551	9609-9615	NN	denotes	XpdTTD
T7546	9616-9623	NNS	denotes	alleles
T7552	9623-9625	,	denotes	,
T7553	9625-9637	RB	denotes	respectively
T7554	9637-9638	.	denotes	.
T7555	9638-9732	sentence	denotes	An ethidium bromide (EtBr)–stained gel showing the amount of total RNA loaded is shown below.
T7556	9639-9641	DT	denotes	An
T7558	9642-9650	NN	denotes	ethidium
T7559	9651-9658	NN	denotes	bromide
T7561	9659-9660	-LRB-	denotes	(
T7562	9660-9664	NN	denotes	EtBr
T7563	9664-9665	-RRB-	denotes	)
T7564	9665-9666	HYPH	denotes	–
T7560	9666-9673	VBN	denotes	stained
T7557	9674-9677	NN	denotes	gel
T7566	9678-9685	VBG	denotes	showing
T7567	9686-9689	DT	denotes	the
T7568	9690-9696	NN	denotes	amount
T7569	9697-9699	IN	denotes	of
T7570	9700-9705	JJ	denotes	total
T7571	9706-9709	NN	denotes	RNA
T7572	9710-9716	VBN	denotes	loaded
T7573	9717-9719	VBZ	denotes	is
T7565	9720-9725	VBN	denotes	shown
T7574	9726-9731	RB	denotes	below
T7575	9731-9732	.	denotes	.
T9211	9742-9751	NN	denotes	Frequency
T9212	9752-9754	IN	denotes	of
T9213	9755-9761	NN	denotes	Xpd†XP
T9215	9761-9762	HYPH	denotes	/
T9214	9762-9765	NN	denotes	†XP
T9216	9765-9767	,	denotes	,
T9217	9767-9775	NN	denotes	Xpd†XPCS
T9219	9775-9776	HYPH	denotes	/
T9218	9776-9781	NN	denotes	†XPCS
T9220	9781-9783	,	denotes	,
T9221	9783-9786	CC	denotes	and
T9222	9787-9795	NN	denotes	Compound
T9224	9796-9808	JJ	denotes	Heterozygous
T9225	9809-9815	NN	denotes	Xpd†XP
T9226	9815-9816	HYPH	denotes	/
T9223	9816-9821	NN	denotes	†XPCS
T9227	9822-9829	NNS	denotes	Embryos
T9228	9830-9833	CC	denotes	and
T9229	9834-9843	NN	denotes	Offspring
T1954	9845-9846	``	denotes	“
T1956	9846-9850	JJ	denotes	Null
T1957	9850-9851	''	denotes	”
T1955	9852-9858	NN	denotes	Allele
T1959	9859-9862	MD	denotes	Can
T1958	9863-9872	VB	denotes	Alleviate
T1960	9873-9886	JJ	denotes	Developmental
T1961	9887-9892	NN	denotes	Delay
T1962	9892-9894	,	denotes	,
T1963	9894-9898	NN	denotes	Skin
T1965	9898-9900	,	denotes	,
T1966	9900-9903	CC	denotes	and
T1967	9904-9908	NN	denotes	Hair
T1964	9909-9917	NNS	denotes	Features
T1968	9918-9920	IN	denotes	of
T1969	9921-9924	NN	denotes	TTD
T1970	9924-10146	sentence	denotes	To test the potential of a homozygous lethal “null” allele to nevertheless contribute to organismal phenotype, we combined an Xpd†XPCS allele with a viable XpdTTD allele by crossing the corresponding heterozygous animals.
T1971	9925-9927	TO	denotes	To
T1972	9928-9932	VB	denotes	test
T1974	9933-9936	DT	denotes	the
T1975	9937-9946	NN	denotes	potential
T1976	9947-9949	IN	denotes	of
T1977	9950-9951	DT	denotes	a
T1979	9952-9962	JJ	denotes	homozygous
T1980	9963-9969	JJ	denotes	lethal
T1981	9970-9971	``	denotes	“
T1982	9971-9975	JJ	denotes	null
T1983	9975-9976	''	denotes	”
T1978	9977-9983	NN	denotes	allele
T1984	9984-9986	TO	denotes	to
T1986	9987-9999	RB	denotes	nevertheless
T1985	10000-10010	VB	denotes	contribute
T1987	10011-10013	IN	denotes	to
T1988	10014-10024	JJ	denotes	organismal
T1989	10025-10034	NN	denotes	phenotype
T1990	10034-10036	,	denotes	,
T1991	10036-10038	PRP	denotes	we
T1973	10039-10047	VBD	denotes	combined
T1992	10048-10050	DT	denotes	an
T1994	10051-10059	NN	denotes	Xpd†XPCS
T1993	10060-10066	NN	denotes	allele
T1995	10067-10071	IN	denotes	with
T1996	10072-10073	DT	denotes	a
T1998	10074-10080	JJ	denotes	viable
T1999	10081-10087	NN	denotes	XpdTTD
T1997	10088-10094	NN	denotes	allele
T2000	10095-10097	IN	denotes	by
T2001	10098-10106	VBG	denotes	crossing
T2002	10107-10110	DT	denotes	the
T2004	10111-10124	VBG	denotes	corresponding
T2005	10125-10137	JJ	denotes	heterozygous
T2003	10138-10145	NNS	denotes	animals
T2006	10145-10146	.	denotes	.
T2007	10146-10317	sentence	denotes	Similar to hemizygous TTD mice carrying one true Xpd knockout allele (XpdTTD/KO), compound heterozygous XpdTTD/†XPCS mice were born at the expected Mendelian frequencies.
T2008	10147-10154	JJ	denotes	Similar
T2010	10155-10157	IN	denotes	to
T2011	10158-10168	JJ	denotes	hemizygous
T2013	10169-10172	NN	denotes	TTD
T2012	10173-10177	NNS	denotes	mice
T2014	10178-10186	VBG	denotes	carrying
T2015	10187-10190	CD	denotes	one
T2017	10191-10195	JJ	denotes	true
T2018	10196-10199	NN	denotes	Xpd
T2019	10200-10208	NN	denotes	knockout
T2016	10209-10215	NN	denotes	allele
T2020	10216-10217	-LRB-	denotes	(
T2022	10217-10223	NN	denotes	XpdTTD
T2023	10223-10224	HYPH	denotes	/
T2021	10224-10226	NN	denotes	KO
T2024	10226-10227	-RRB-	denotes	)
T2025	10227-10229	,	denotes	,
T2026	10229-10237	NN	denotes	compound
T2028	10238-10250	JJ	denotes	heterozygous
T2029	10251-10257	NN	denotes	XpdTTD
T2031	10257-10258	HYPH	denotes	/
T2030	10258-10263	NN	denotes	†XPCS
T2027	10264-10268	NNS	denotes	mice
T2032	10269-10273	VBD	denotes	were
T2009	10274-10278	VBN	denotes	born
T2033	10279-10281	IN	denotes	at
T2034	10282-10285	DT	denotes	the
T2036	10286-10294	VBN	denotes	expected
T2037	10295-10304	JJ	denotes	Mendelian
T2035	10305-10316	NNS	denotes	frequencies
T2038	10316-10317	.	denotes	.
T2039	10317-10513	sentence	denotes	Expression from the Xpd†XPCS allele was also reduced in the testis of compound heterozygous animals, whereas expression from the XpdTTD allele was increased relative to wt by ~5-fold (Figure 1E).
T2040	10318-10328	NN	denotes	Expression
T2042	10329-10333	IN	denotes	from
T2043	10334-10337	DT	denotes	the
T2045	10338-10346	NN	denotes	Xpd†XPCS
T2044	10347-10353	NN	denotes	allele
T2046	10354-10357	VBD	denotes	was
T2047	10358-10362	RB	denotes	also
T2041	10363-10370	VBN	denotes	reduced
T2048	10371-10373	IN	denotes	in
T2049	10374-10377	DT	denotes	the
T2050	10378-10384	NN	denotes	testis
T2051	10385-10387	IN	denotes	of
T2052	10388-10396	NN	denotes	compound
T2054	10397-10409	JJ	denotes	heterozygous
T2053	10410-10417	NNS	denotes	animals
T2055	10417-10419	,	denotes	,
T2056	10419-10426	IN	denotes	whereas
T2058	10427-10437	NN	denotes	expression
T2059	10438-10442	IN	denotes	from
T2060	10443-10446	DT	denotes	the
T2062	10447-10453	NN	denotes	XpdTTD
T2061	10454-10460	NN	denotes	allele
T2063	10461-10464	VBD	denotes	was
T2057	10465-10474	VBN	denotes	increased
T2064	10475-10483	JJ	denotes	relative
T2065	10484-10486	IN	denotes	to
T2066	10487-10489	NN	denotes	wt
T2067	10490-10492	IN	denotes	by
T2068	10493-10494	SYM	denotes	~
T2069	10494-10500	RB	denotes	5-fold
T2070	10501-10502	-LRB-	denotes	(
T2072	10502-10508	NN	denotes	Figure
T2071	10509-10511	NN	denotes	1E
T2073	10511-10512	-RRB-	denotes	)
T2074	10512-10513	.	denotes	.
T2075	10513-10766	sentence	denotes	Because of a lack of available antibodies and the inability to distinguish amongst various mutant forms of XPD differing only by single amino acid substitutions, we were unable to ascertain the relative amount of XPD protein from the different alleles.
T2076	10514-10521	IN	denotes	Because
T2078	10522-10524	IN	denotes	of
T2079	10525-10526	DT	denotes	a
T2080	10527-10531	NN	denotes	lack
T2081	10532-10534	IN	denotes	of
T2082	10535-10544	JJ	denotes	available
T2083	10545-10555	NNS	denotes	antibodies
T2084	10556-10559	CC	denotes	and
T2085	10560-10563	DT	denotes	the
T2086	10564-10573	NN	denotes	inability
T2087	10574-10576	TO	denotes	to
T2088	10577-10588	VB	denotes	distinguish
T2089	10589-10596	IN	denotes	amongst
T2090	10597-10604	JJ	denotes	various
T2092	10605-10611	JJ	denotes	mutant
T2091	10612-10617	NNS	denotes	forms
T2093	10618-10620	IN	denotes	of
T2094	10621-10624	NN	denotes	XPD
T2095	10625-10634	VBG	denotes	differing
T2096	10635-10639	RB	denotes	only
T2097	10640-10642	IN	denotes	by
T2098	10643-10649	JJ	denotes	single
T2100	10650-10655	NN	denotes	amino
T2101	10656-10660	NN	denotes	acid
T2099	10661-10674	NNS	denotes	substitutions
T2102	10674-10676	,	denotes	,
T2103	10676-10678	PRP	denotes	we
T2077	10679-10683	VBD	denotes	were
T2104	10684-10690	JJ	denotes	unable
T2105	10691-10693	TO	denotes	to
T2106	10694-10703	VB	denotes	ascertain
T2107	10704-10707	DT	denotes	the
T2109	10708-10716	JJ	denotes	relative
T2108	10717-10723	NN	denotes	amount
T2110	10724-10726	IN	denotes	of
T2111	10727-10730	NN	denotes	XPD
T2112	10731-10738	NN	denotes	protein
T2113	10739-10743	IN	denotes	from
T2114	10744-10747	DT	denotes	the
T2116	10748-10757	JJ	denotes	different
T2115	10758-10765	NNS	denotes	alleles
T2117	10765-10766	.	denotes	.
T2118	10766-11073	sentence	denotes	Despite reduced levels of mRNA expression, the homozygous lethal Xpd†XPCS allele ameliorated multiple XpdTTD-associated disease symptoms in compound heterozygous XpdTTD/†XPCS animals including the hallmark brittle hair and cutaneous features fully penetrant in homo- and hemizygous TTD mice (Figure 2A–2C).
T2119	10767-10774	IN	denotes	Despite
T2121	10775-10782	VBN	denotes	reduced
T2122	10783-10789	NNS	denotes	levels
T2123	10790-10792	IN	denotes	of
T2124	10793-10797	NN	denotes	mRNA
T2125	10798-10808	NN	denotes	expression
T2126	10808-10810	,	denotes	,
T2127	10810-10813	DT	denotes	the
T2129	10814-10824	JJ	denotes	homozygous
T2130	10825-10831	JJ	denotes	lethal
T2131	10832-10840	NN	denotes	Xpd†XPCS
T2128	10841-10847	NN	denotes	allele
T2120	10848-10859	VBD	denotes	ameliorated
T2132	10860-10868	JJ	denotes	multiple
T2134	10869-10875	NN	denotes	XpdTTD
T2136	10875-10876	HYPH	denotes	-
T2135	10876-10886	JJ	denotes	associated
T2137	10887-10894	NN	denotes	disease
T2133	10895-10903	NNS	denotes	symptoms
T2138	10904-10906	IN	denotes	in
T2139	10907-10915	JJ	denotes	compound
T2141	10916-10928	JJ	denotes	heterozygous
T2142	10929-10935	NN	denotes	XpdTTD
T2144	10935-10936	HYPH	denotes	/
T2143	10936-10941	NN	denotes	†XPCS
T2140	10942-10949	NNS	denotes	animals
T2145	10950-10959	VBG	denotes	including
T2146	10960-10963	DT	denotes	the
T2148	10964-10972	NN	denotes	hallmark
T2149	10973-10980	JJ	denotes	brittle
T2147	10981-10985	NN	denotes	hair
T2150	10986-10989	CC	denotes	and
T2151	10990-10999	JJ	denotes	cutaneous
T2152	11000-11008	NNS	denotes	features
T2153	11009-11014	RB	denotes	fully
T2154	11015-11024	JJ	denotes	penetrant
T2155	11025-11027	IN	denotes	in
T2156	11028-11032	AFX	denotes	homo
T2158	11032-11033	HYPH	denotes	-
T2159	11034-11037	CC	denotes	and
T2157	11038-11048	JJ	denotes	hemizygous
T2161	11049-11052	NN	denotes	TTD
T2160	11053-11057	NNS	denotes	mice
T2162	11058-11059	-LRB-	denotes	(
T2164	11059-11065	NN	denotes	Figure
T2163	11066-11068	NN	denotes	2A
T2165	11068-11069	SYM	denotes	–
T2166	11069-11071	NN	denotes	2C
T2167	11071-11072	-RRB-	denotes	)
T2168	11072-11073	.	denotes	.
T2169	11073-11397	sentence	denotes	In marked contrast to XpdTTD/TTD (and XpdTTD/KO) mice, which display complete hair loss in the first hair cycle and partial hair loss in subsequent cycles throughout their lives [21], compound heterozygous XpdTTD/†XPCS mice displayed some hair loss only during the first hair cycle and only locally at the back (Figure 2A).
T2170	11074-11076	IN	denotes	In
T2172	11077-11083	JJ	denotes	marked
T2173	11084-11092	NN	denotes	contrast
T2174	11093-11095	IN	denotes	to
T2175	11096-11102	NN	denotes	XpdTTD
T2177	11102-11103	HYPH	denotes	/
T2176	11103-11106	NN	denotes	TTD
T2179	11107-11108	-LRB-	denotes	(
T2180	11108-11111	CC	denotes	and
T2181	11112-11118	NN	denotes	XpdTTD
T2183	11118-11119	HYPH	denotes	/
T2182	11119-11121	NN	denotes	KO
T2184	11121-11122	-RRB-	denotes	)
T2178	11123-11127	NNS	denotes	mice
T2185	11127-11129	,	denotes	,
T2186	11129-11134	WDT	denotes	which
T2187	11135-11142	VBP	denotes	display
T2188	11143-11151	JJ	denotes	complete
T2190	11152-11156	NN	denotes	hair
T2189	11157-11161	NN	denotes	loss
T2191	11162-11164	IN	denotes	in
T2192	11165-11168	DT	denotes	the
T2194	11169-11174	JJ	denotes	first
T2195	11175-11179	NN	denotes	hair
T2193	11180-11185	NN	denotes	cycle
T2196	11186-11189	CC	denotes	and
T2197	11190-11197	JJ	denotes	partial
T2199	11198-11202	NN	denotes	hair
T2198	11203-11207	NN	denotes	loss
T2200	11208-11210	IN	denotes	in
T2201	11211-11221	JJ	denotes	subsequent
T2202	11222-11228	NNS	denotes	cycles
T2203	11229-11239	IN	denotes	throughout
T2204	11240-11245	PRP$	denotes	their
T2205	11246-11251	NNS	denotes	lives
T2206	11252-11253	-LRB-	denotes	[
T2207	11253-11255	CD	denotes	21
T2208	11255-11256	-RRB-	denotes	]
T2209	11256-11258	,	denotes	,
T2210	11258-11266	NN	denotes	compound
T2212	11267-11279	JJ	denotes	heterozygous
T2213	11280-11292	NN	denotes	XpdTTD/†XPCS
T2211	11293-11297	NNS	denotes	mice
T2171	11298-11307	VBD	denotes	displayed
T2214	11308-11312	DT	denotes	some
T2216	11313-11317	NN	denotes	hair
T2215	11318-11322	NN	denotes	loss
T2217	11323-11327	RB	denotes	only
T2218	11328-11334	IN	denotes	during
T2219	11335-11338	DT	denotes	the
T2221	11339-11344	JJ	denotes	first
T2222	11345-11349	NN	denotes	hair
T2220	11350-11355	NN	denotes	cycle
T2223	11356-11359	CC	denotes	and
T2224	11360-11364	RB	denotes	only
T2225	11365-11372	RB	denotes	locally
T2226	11373-11375	IN	denotes	at
T2227	11376-11379	DT	denotes	the
T2228	11380-11384	NN	denotes	back
T2229	11385-11386	-LRB-	denotes	(
T2231	11386-11392	NN	denotes	Figure
T2230	11393-11395	NN	denotes	2A
T2232	11395-11396	-RRB-	denotes	)
T2233	11396-11397	.	denotes	.
T2234	11397-11591	sentence	denotes	Scanning electron microscope analysis of XpdTTD/†XPCS hair revealed an almost normal appearance, with TTD-like features such as broken hairs found only at very low frequency (unpublished data).
T2235	11398-11406	NN	denotes	Scanning
T2237	11407-11415	NN	denotes	electron
T2236	11416-11426	NN	denotes	microscope
T2238	11427-11435	NN	denotes	analysis
T2240	11436-11438	IN	denotes	of
T2241	11439-11445	NN	denotes	XpdTTD
T2243	11445-11446	HYPH	denotes	/
T2242	11446-11451	NN	denotes	†XPCS
T2244	11452-11456	NN	denotes	hair
T2239	11457-11465	VBD	denotes	revealed
T2245	11466-11468	DT	denotes	an
T2247	11469-11475	RB	denotes	almost
T2248	11476-11482	JJ	denotes	normal
T2246	11483-11493	NN	denotes	appearance
T2249	11493-11495	,	denotes	,
T2250	11495-11499	IN	denotes	with
T2251	11500-11503	NN	denotes	TTD
T2253	11503-11504	HYPH	denotes	-
T2252	11504-11508	JJ	denotes	like
T2254	11509-11517	NNS	denotes	features
T2255	11518-11522	JJ	denotes	such
T2256	11523-11525	IN	denotes	as
T2257	11526-11532	JJ	denotes	broken
T2258	11533-11538	NNS	denotes	hairs
T2259	11539-11544	VBN	denotes	found
T2260	11545-11549	RB	denotes	only
T2261	11550-11552	IN	denotes	at
T2262	11553-11557	RB	denotes	very
T2263	11558-11561	JJ	denotes	low
T2264	11562-11571	NN	denotes	frequency
T2265	11572-11573	-LRB-	denotes	(
T2267	11573-11584	JJ	denotes	unpublished
T2266	11585-11589	NNS	denotes	data
T2268	11589-11590	-RRB-	denotes	)
T2269	11590-11591	.	denotes	.
T2270	11591-11778	sentence	denotes	Amino acid analysis confirmed that cysteine levels in the hair of the XpdTTD/†XPCS mice were significantly higher than in XpdTTD/TTD animals, but remained below the wt level (Figure 2C).
T2271	11592-11597	NN	denotes	Amino
T2272	11598-11602	NN	denotes	acid
T2273	11603-11611	NN	denotes	analysis
T2274	11612-11621	VBD	denotes	confirmed
T2275	11622-11626	IN	denotes	that
T2277	11627-11635	NN	denotes	cysteine
T2278	11636-11642	NNS	denotes	levels
T2279	11643-11645	IN	denotes	in
T2280	11646-11649	DT	denotes	the
T2281	11650-11654	NN	denotes	hair
T2282	11655-11657	IN	denotes	of
T2283	11658-11661	DT	denotes	the
T2285	11662-11668	NN	denotes	XpdTTD
T2287	11668-11669	HYPH	denotes	/
T2286	11669-11674	NN	denotes	†XPCS
T2284	11675-11679	NNS	denotes	mice
T2276	11680-11684	VBD	denotes	were
T2288	11685-11698	RB	denotes	significantly
T2289	11699-11705	JJR	denotes	higher
T2290	11706-11710	IN	denotes	than
T2291	11711-11713	IN	denotes	in
T2292	11714-11720	NN	denotes	XpdTTD
T2294	11720-11721	HYPH	denotes	/
T2293	11721-11724	NN	denotes	TTD
T2295	11725-11732	NNS	denotes	animals
T2296	11732-11734	,	denotes	,
T2297	11734-11737	CC	denotes	but
T2298	11738-11746	VBD	denotes	remained
T2299	11747-11752	IN	denotes	below
T2300	11753-11756	DT	denotes	the
T2302	11757-11759	NN	denotes	wt
T2301	11760-11765	NN	denotes	level
T2303	11766-11767	-LRB-	denotes	(
T2305	11767-11773	NN	denotes	Figure
T2304	11774-11776	NN	denotes	2C
T2306	11776-11777	-RRB-	denotes	)
T2307	11777-11778	.	denotes	.
T2308	11778-11926	sentence	denotes	TTD hemizygotes (XpdTTD/KO) do not display significant differences in cutaneous features and longevity relative to homozygous XpdTTD/TTD mice [21].
T2309	11779-11782	NN	denotes	TTD
T2310	11783-11794	NNS	denotes	hemizygotes
T2312	11795-11796	-LRB-	denotes	(
T2314	11796-11802	NN	denotes	XpdTTD
T2315	11802-11803	HYPH	denotes	/
T2313	11803-11805	NN	denotes	KO
T2316	11805-11806	-RRB-	denotes	)
T2317	11807-11809	VBP	denotes	do
T2318	11810-11813	RB	denotes	not
T2311	11814-11821	VB	denotes	display
T2319	11822-11833	JJ	denotes	significant
T2320	11834-11845	NNS	denotes	differences
T2321	11846-11848	IN	denotes	in
T2322	11849-11858	JJ	denotes	cutaneous
T2323	11859-11867	NNS	denotes	features
T2324	11868-11871	CC	denotes	and
T2325	11872-11881	NN	denotes	longevity
T2326	11882-11890	JJ	denotes	relative
T2327	11891-11893	IN	denotes	to
T2328	11894-11904	JJ	denotes	homozygous
T2330	11905-11911	NN	denotes	XpdTTD
T2332	11911-11912	HYPH	denotes	/
T2331	11912-11915	NN	denotes	TTD
T2329	11916-11920	NNS	denotes	mice
T2333	11921-11922	-LRB-	denotes	[
T2334	11922-11924	CD	denotes	21
T2335	11924-11925	-RRB-	denotes	]
T2336	11925-11926	.	denotes	.
T2337	11926-13586	sentence	denotes	Figure 2 Partial Rescue of TTD Cutaneous, Blood, and Developmental Phenotypes in Compound Heterozygous XpdTTD/†XPCS Mice (A) Photographs of 5-mo-old homozygous XpdTTD/TTD, compound heterozygous XpdTTD/†XPCS, and wt mice. Insets: images of first-round hair loss. (B) Histological analysis of the skin of XpdTTD/TTD, XpdTTD/†XPCS, and wt mice. TTD-associated acanthosis (thicker epidermis, indicated by solid vertical line), pronounced granular layer (indicated by arrows), and sebacious gland hyperplasia (indicated by dotted vertical line) were absent in the epidermis of XpdTTD/†XPCS and wt mice. Magnification 400×. (C) Cysteine content of hair from wt, XpdTTD/TTD, and XpdTTD/†XPCS mice. The p-value indicates significant differences between mutants and wt, as well as between XpdTTD/TTD and XpdTTD/†XPCS mice. Error bars indicate standard error of the mean (SEM). (D) Hematocrit values from blood of XpdTTD/TTD and XpdTTD/†XPCS mice. The p-values indicate the significance of the difference relative to wt. Error bars indicate SEM. (E) Body weights of developing XpdTTD/TTD and XpdTTD/†XPCS mice after weaning plotted as a percentage of the weight of age-matched control wt and heterozygote (hz) littermates (set at 100%). Error bars indicate SEM. Other prominent TTD features in the epidermis, including acanthosis (thickening of the layer of the nucleated cells), hyperkeratosis (prominent thickening of the cornified layer), and pronounced granular layer and sebacious gland hyperplasia (causing greasy appearance of the hair), were absent in the skin of XpdTTD/†XPCS mice, as established by blind microscopic examination of skin sections (Figure 2B).
T7658	11937-11944	JJ	denotes	Partial
T7659	11945-11951	NN	denotes	Rescue
T7660	11952-11954	IN	denotes	of
T7661	11955-11958	NN	denotes	TTD
T7662	11959-11968	JJ	denotes	Cutaneous
T7663	11968-11970	,	denotes	,
T7664	11970-11975	NN	denotes	Blood
T7665	11975-11977	,	denotes	,
T7666	11977-11980	CC	denotes	and
T7667	11981-11994	JJ	denotes	Developmental
T7668	11995-12005	NNS	denotes	Phenotypes
T7669	12006-12008	IN	denotes	in
T7670	12009-12017	NN	denotes	Compound
T7672	12018-12030	JJ	denotes	Heterozygous
T7673	12031-12037	NN	denotes	XpdTTD
T7675	12037-12038	HYPH	denotes	/
T7674	12038-12043	NN	denotes	†XPCS
T7671	12044-12048	NNS	denotes	Mice
T7676	12048-12148	sentence	denotes	(A) Photographs of 5-mo-old homozygous XpdTTD/TTD, compound heterozygous XpdTTD/†XPCS, and wt mice.
T7677	12049-12050	-LRB-	denotes	(
T7678	12050-12051	LS	denotes	A
T7680	12051-12052	-RRB-	denotes	)
T7679	12053-12064	NNS	denotes	Photographs
T7681	12065-12067	IN	denotes	of
T7682	12068-12069	CD	denotes	5
T7684	12069-12070	HYPH	denotes	-
T7683	12070-12072	NN	denotes	mo
T7686	12072-12073	HYPH	denotes	-
T7685	12073-12076	JJ	denotes	old
T7688	12077-12087	JJ	denotes	homozygous
T7690	12088-12094	NN	denotes	XpdTTD
T7691	12094-12095	HYPH	denotes	/
T7689	12095-12098	NN	denotes	TTD
T7692	12098-12100	,	denotes	,
T7693	12100-12108	NN	denotes	compound
T7695	12109-12121	JJ	denotes	heterozygous
T7696	12122-12128	NN	denotes	XpdTTD
T7697	12128-12129	HYPH	denotes	/
T7694	12129-12134	NN	denotes	†XPCS
T7698	12134-12136	,	denotes	,
T7699	12136-12139	CC	denotes	and
T7700	12140-12142	NN	denotes	wt
T7687	12143-12147	NNS	denotes	mice
T7701	12147-12148	.	denotes	.
T7702	12148-12189	sentence	denotes	Insets: images of first-round hair loss.
T7703	12149-12155	NNS	denotes	Insets
T7704	12155-12157	:	denotes	:
T7705	12157-12163	NNS	denotes	images
T7706	12164-12166	IN	denotes	of
T7707	12167-12172	JJ	denotes	first
T7709	12172-12173	HYPH	denotes	-
T7708	12173-12178	NN	denotes	round
T7711	12179-12183	NN	denotes	hair
T7710	12184-12188	NN	denotes	loss
T7712	12188-12189	.	denotes	.
T7713	12189-12269	sentence	denotes	(B) Histological analysis of the skin of XpdTTD/TTD, XpdTTD/†XPCS, and wt mice.
T7714	12190-12191	-LRB-	denotes	(
T7715	12191-12192	LS	denotes	B
T7717	12192-12193	-RRB-	denotes	)
T7718	12194-12206	JJ	denotes	Histological
T7716	12207-12215	NN	denotes	analysis
T7719	12216-12218	IN	denotes	of
T7720	12219-12222	DT	denotes	the
T7721	12223-12227	NN	denotes	skin
T7722	12228-12230	IN	denotes	of
T7723	12231-12237	NN	denotes	XpdTTD
T7725	12237-12238	HYPH	denotes	/
T7724	12238-12241	NN	denotes	TTD
T7727	12241-12243	,	denotes	,
T7728	12243-12249	NN	denotes	XpdTTD
T7730	12249-12250	HYPH	denotes	/
T7729	12250-12255	NN	denotes	†XPCS
T7731	12255-12257	,	denotes	,
T7732	12257-12260	CC	denotes	and
T7733	12261-12263	NN	denotes	wt
T7726	12264-12268	NNS	denotes	mice
T7734	12268-12269	.	denotes	.
T7735	12269-12525	sentence	denotes	TTD-associated acanthosis (thicker epidermis, indicated by solid vertical line), pronounced granular layer (indicated by arrows), and sebacious gland hyperplasia (indicated by dotted vertical line) were absent in the epidermis of XpdTTD/†XPCS and wt mice.
T7736	12270-12273	NN	denotes	TTD
T7738	12273-12274	HYPH	denotes	-
T7737	12274-12284	JJ	denotes	associated
T7739	12285-12295	NN	denotes	acanthosis
T7741	12296-12297	-LRB-	denotes	(
T7743	12297-12304	JJR	denotes	thicker
T7742	12305-12314	NN	denotes	epidermis
T7744	12314-12316	,	denotes	,
T7745	12316-12325	VBN	denotes	indicated
T7746	12326-12328	IN	denotes	by
T7747	12329-12334	JJ	denotes	solid
T7749	12335-12343	JJ	denotes	vertical
T7748	12344-12348	NN	denotes	line
T7750	12348-12349	-RRB-	denotes	)
T7751	12349-12351	,	denotes	,
T7752	12351-12361	VBN	denotes	pronounced
T7754	12362-12370	JJ	denotes	granular
T7753	12371-12376	NN	denotes	layer
T7755	12377-12378	-LRB-	denotes	(
T7756	12378-12387	VBN	denotes	indicated
T7757	12388-12390	IN	denotes	by
T7758	12391-12397	NNS	denotes	arrows
T7759	12397-12398	-RRB-	denotes	)
T7760	12398-12400	,	denotes	,
T7761	12400-12403	CC	denotes	and
T7762	12404-12413	JJ	denotes	sebacious
T7764	12414-12419	NN	denotes	gland
T7763	12420-12431	NN	denotes	hyperplasia
T7765	12432-12433	-LRB-	denotes	(
T7766	12433-12442	VBN	denotes	indicated
T7767	12443-12445	IN	denotes	by
T7768	12446-12452	VBN	denotes	dotted
T7770	12453-12461	JJ	denotes	vertical
T7769	12462-12466	NN	denotes	line
T7771	12466-12467	-RRB-	denotes	)
T7740	12468-12472	VBD	denotes	were
T7772	12473-12479	JJ	denotes	absent
T7773	12480-12482	IN	denotes	in
T7774	12483-12486	DT	denotes	the
T7775	12487-12496	NN	denotes	epidermis
T7776	12497-12499	IN	denotes	of
T7777	12500-12506	NN	denotes	XpdTTD
T7779	12506-12507	HYPH	denotes	/
T7778	12507-12512	NN	denotes	†XPCS
T7781	12513-12516	CC	denotes	and
T7782	12517-12519	NN	denotes	wt
T7780	12520-12524	NNS	denotes	mice
T7783	12524-12525	.	denotes	.
T7784	12525-12545	sentence	denotes	Magnification 400×.
T7785	12526-12539	NN	denotes	Magnification
T7786	12540-12543	CD	denotes	400
T7787	12543-12544	SYM	denotes	×
T7788	12544-12545	.	denotes	.
T7789	12545-12618	sentence	denotes	(C) Cysteine content of hair from wt, XpdTTD/TTD, and XpdTTD/†XPCS mice.
T7790	12546-12547	-LRB-	denotes	(
T7791	12547-12548	LS	denotes	C
T7793	12548-12549	-RRB-	denotes	)
T7794	12550-12558	NN	denotes	Cysteine
T7792	12559-12566	NN	denotes	content
T7795	12567-12569	IN	denotes	of
T7796	12570-12574	NN	denotes	hair
T7797	12575-12579	IN	denotes	from
T7798	12580-12582	NN	denotes	wt
T7800	12582-12584	,	denotes	,
T7801	12584-12590	NN	denotes	XpdTTD
T7803	12590-12591	HYPH	denotes	/
T7802	12591-12594	NN	denotes	TTD
T7804	12594-12596	,	denotes	,
T7805	12596-12599	CC	denotes	and
T7806	12600-12606	NN	denotes	XpdTTD
T7808	12606-12607	HYPH	denotes	/
T7807	12607-12612	NN	denotes	†XPCS
T7799	12613-12617	NNS	denotes	mice
T7809	12617-12618	.	denotes	.
T7810	12618-12741	sentence	denotes	The p-value indicates significant differences between mutants and wt, as well as between XpdTTD/TTD and XpdTTD/†XPCS mice.
T7811	12619-12622	DT	denotes	The
T7813	12623-12624	NN	denotes	p
T7814	12624-12625	HYPH	denotes	-
T7812	12625-12630	NN	denotes	value
T7815	12631-12640	VBZ	denotes	indicates
T7816	12641-12652	JJ	denotes	significant
T7817	12653-12664	NNS	denotes	differences
T7818	12665-12672	IN	denotes	between
T7819	12673-12680	NNS	denotes	mutants
T7820	12681-12684	CC	denotes	and
T7821	12685-12687	NN	denotes	wt
T7822	12687-12689	,	denotes	,
T7823	12689-12691	RB	denotes	as
T7825	12692-12696	RB	denotes	well
T7824	12697-12699	IN	denotes	as
T7826	12700-12707	IN	denotes	between
T7827	12708-12714	NN	denotes	XpdTTD
T7829	12714-12715	HYPH	denotes	/
T7828	12715-12718	NN	denotes	TTD
T7831	12719-12722	CC	denotes	and
T7832	12723-12729	NN	denotes	XpdTTD
T7834	12729-12730	HYPH	denotes	/
T7833	12730-12735	NN	denotes	†XPCS
T7830	12736-12740	NNS	denotes	mice
T7835	12740-12741	.	denotes	.
T7836	12741-12795	sentence	denotes	Error bars indicate standard error of the mean (SEM).
T7837	12742-12747	NN	denotes	Error
T7838	12748-12752	NNS	denotes	bars
T7839	12753-12761	VBP	denotes	indicate
T7840	12762-12770	JJ	denotes	standard
T7841	12771-12776	NN	denotes	error
T7842	12777-12779	IN	denotes	of
T7843	12780-12783	DT	denotes	the
T7844	12784-12788	NN	denotes	mean
T7845	12789-12790	-LRB-	denotes	(
T7846	12790-12793	NN	denotes	SEM
T7847	12793-12794	-RRB-	denotes	)
T7848	12794-12795	.	denotes	.
T7849	12795-12865	sentence	denotes	(D) Hematocrit values from blood of XpdTTD/TTD and XpdTTD/†XPCS mice.
T7850	12796-12797	-LRB-	denotes	(
T7851	12797-12798	LS	denotes	D
T7853	12798-12799	-RRB-	denotes	)
T7854	12800-12810	NN	denotes	Hematocrit
T7852	12811-12817	NNS	denotes	values
T7855	12818-12822	IN	denotes	from
T7856	12823-12828	NN	denotes	blood
T7857	12829-12831	IN	denotes	of
T7858	12832-12838	NN	denotes	XpdTTD
T7860	12838-12839	HYPH	denotes	/
T7859	12839-12842	NN	denotes	TTD
T7862	12843-12846	CC	denotes	and
T7863	12847-12853	NN	denotes	XpdTTD
T7865	12853-12854	HYPH	denotes	/
T7864	12854-12859	NN	denotes	†XPCS
T7861	12860-12864	NNS	denotes	mice
T7866	12864-12865	.	denotes	.
T7867	12865-12938	sentence	denotes	The p-values indicate the significance of the difference relative to wt.
T7868	12866-12869	DT	denotes	The
T7870	12870-12871	NN	denotes	p
T7871	12871-12872	HYPH	denotes	-
T7869	12872-12878	NNS	denotes	values
T7872	12879-12887	VBP	denotes	indicate
T7873	12888-12891	DT	denotes	the
T7874	12892-12904	NN	denotes	significance
T7875	12905-12907	IN	denotes	of
T7876	12908-12911	DT	denotes	the
T7877	12912-12922	NN	denotes	difference
T7878	12923-12931	JJ	denotes	relative
T7879	12932-12934	IN	denotes	to
T7880	12935-12937	NN	denotes	wt
T7881	12937-12938	.	denotes	.
T7882	12938-12963	sentence	denotes	Error bars indicate SEM.
T7883	12939-12944	NN	denotes	Error
T7884	12945-12949	NNS	denotes	bars
T7885	12950-12958	VBP	denotes	indicate
T7886	12959-12962	NN	denotes	SEM
T7887	12962-12963	.	denotes	.
T7888	12963-13154	sentence	denotes	(E) Body weights of developing XpdTTD/TTD and XpdTTD/†XPCS mice after weaning plotted as a percentage of the weight of age-matched control wt and heterozygote (hz) littermates (set at 100%).
T7889	12964-12965	-LRB-	denotes	(
T7890	12965-12966	LS	denotes	E
T7892	12966-12967	-RRB-	denotes	)
T7893	12968-12972	NN	denotes	Body
T7891	12973-12980	NNS	denotes	weights
T7894	12981-12983	IN	denotes	of
T7895	12984-12994	VBG	denotes	developing
T7897	12995-13001	NN	denotes	XpdTTD
T7899	13001-13002	HYPH	denotes	/
T7898	13002-13005	NN	denotes	TTD
T7900	13006-13009	CC	denotes	and
T7901	13010-13016	NN	denotes	XpdTTD
T7903	13016-13017	HYPH	denotes	/
T7902	13017-13022	NN	denotes	†XPCS
T7896	13023-13027	NNS	denotes	mice
T7904	13028-13033	IN	denotes	after
T7905	13034-13041	VBG	denotes	weaning
T7906	13042-13049	VBN	denotes	plotted
T7907	13050-13052	IN	denotes	as
T7908	13053-13054	DT	denotes	a
T7909	13055-13065	NN	denotes	percentage
T7910	13066-13068	IN	denotes	of
T7911	13069-13072	DT	denotes	the
T7912	13073-13079	NN	denotes	weight
T7913	13080-13082	IN	denotes	of
T7914	13083-13086	NN	denotes	age
T7916	13086-13087	HYPH	denotes	-
T7915	13087-13094	JJ	denotes	matched
T7918	13095-13102	NN	denotes	control
T7919	13103-13105	NN	denotes	wt
T7920	13106-13109	CC	denotes	and
T7921	13110-13122	NN	denotes	heterozygote
T7922	13123-13124	-LRB-	denotes	(
T7923	13124-13126	NN	denotes	hz
T7924	13126-13127	-RRB-	denotes	)
T7917	13128-13139	NNS	denotes	littermates
T7925	13140-13141	-LRB-	denotes	(
T7926	13141-13144	VBN	denotes	set
T7927	13145-13147	IN	denotes	at
T7928	13148-13151	CD	denotes	100
T7929	13151-13152	NN	denotes	%
T7930	13152-13153	-RRB-	denotes	)
T7931	13153-13154	.	denotes	.
T7932	13154-13179	sentence	denotes	Error bars indicate SEM.
T7933	13155-13160	NN	denotes	Error
T7934	13161-13165	NNS	denotes	bars
T7935	13166-13174	VBP	denotes	indicate
T7936	13175-13178	NN	denotes	SEM
T7937	13178-13179	.	denotes	.
T2338	13180-13185	JJ	denotes	Other
T2340	13186-13195	JJ	denotes	prominent
T2341	13196-13199	NN	denotes	TTD
T2339	13200-13208	NNS	denotes	features
T2343	13209-13211	IN	denotes	in
T2344	13212-13215	DT	denotes	the
T2345	13216-13225	NN	denotes	epidermis
T2346	13225-13227	,	denotes	,
T2347	13227-13236	VBG	denotes	including
T2348	13237-13247	NN	denotes	acanthosis
T2349	13248-13249	-LRB-	denotes	(
T2350	13249-13259	VBG	denotes	thickening
T2351	13260-13262	IN	denotes	of
T2352	13263-13266	DT	denotes	the
T2353	13267-13272	NN	denotes	layer
T2354	13273-13275	IN	denotes	of
T2355	13276-13279	DT	denotes	the
T2357	13280-13289	JJ	denotes	nucleated
T2356	13290-13295	NNS	denotes	cells
T2358	13295-13296	-RRB-	denotes	)
T2359	13296-13298	,	denotes	,
T2360	13298-13312	NN	denotes	hyperkeratosis
T2361	13313-13314	-LRB-	denotes	(
T2363	13314-13323	JJ	denotes	prominent
T2362	13324-13334	NN	denotes	thickening
T2364	13335-13337	IN	denotes	of
T2365	13338-13341	DT	denotes	the
T2367	13342-13351	VBN	denotes	cornified
T2366	13352-13357	NN	denotes	layer
T2368	13357-13358	-RRB-	denotes	)
T2369	13358-13360	,	denotes	,
T2370	13360-13363	CC	denotes	and
T2371	13364-13374	JJ	denotes	pronounced
T2373	13375-13383	JJ	denotes	granular
T2372	13384-13389	NN	denotes	layer
T2374	13390-13393	CC	denotes	and
T2375	13394-13403	JJ	denotes	sebacious
T2376	13404-13409	NN	denotes	gland
T2377	13410-13421	NN	denotes	hyperplasia
T2378	13422-13423	-LRB-	denotes	(
T2379	13423-13430	VBG	denotes	causing
T2380	13431-13437	JJ	denotes	greasy
T2381	13438-13448	NN	denotes	appearance
T2382	13449-13451	IN	denotes	of
T2383	13452-13455	DT	denotes	the
T2384	13456-13460	NN	denotes	hair
T2385	13460-13461	-RRB-	denotes	)
T2386	13461-13463	,	denotes	,
T2342	13463-13467	VBD	denotes	were
T2387	13468-13474	JJ	denotes	absent
T2388	13475-13477	IN	denotes	in
T2389	13478-13481	DT	denotes	the
T2390	13482-13486	NN	denotes	skin
T2391	13487-13489	IN	denotes	of
T2392	13490-13496	NN	denotes	XpdTTD
T2394	13496-13497	HYPH	denotes	/
T2393	13497-13502	NN	denotes	†XPCS
T2395	13503-13507	NNS	denotes	mice
T2396	13507-13509	,	denotes	,
T2397	13509-13511	IN	denotes	as
T2398	13512-13523	VBN	denotes	established
T2399	13524-13526	IN	denotes	by
T2400	13527-13532	JJ	denotes	blind
T2402	13533-13544	JJ	denotes	microscopic
T2401	13545-13556	NN	denotes	examination
T2403	13557-13559	IN	denotes	of
T2404	13560-13564	NN	denotes	skin
T2405	13565-13573	NNS	denotes	sections
T2406	13574-13575	-LRB-	denotes	(
T2408	13575-13581	NN	denotes	Figure
T2407	13582-13584	NN	denotes	2B
T2409	13584-13585	-RRB-	denotes	)
T2410	13585-13586	.	denotes	.
T2411	13586-13784	sentence	denotes	Furthermore, anaemia and developmental delay present in patients with TTD [24] and in XpdTTD/TTD mice [15] were both partially rescued in compound heterozygous XpdTTD/†XPCS mice (Figure 2D and 2E).
T2412	13587-13598	RB	denotes	Furthermore
T2414	13598-13600	,	denotes	,
T2415	13600-13607	NN	denotes	anaemia
T2416	13608-13611	CC	denotes	and
T2417	13612-13625	JJ	denotes	developmental
T2418	13626-13631	NN	denotes	delay
T2419	13632-13639	JJ	denotes	present
T2420	13640-13642	IN	denotes	in
T2421	13643-13651	NNS	denotes	patients
T2422	13652-13656	IN	denotes	with
T2423	13657-13660	NN	denotes	TTD
T2424	13661-13662	-LRB-	denotes	[
T2425	13662-13664	CD	denotes	24
T2426	13664-13665	-RRB-	denotes	]
T2427	13666-13669	CC	denotes	and
T2428	13670-13672	IN	denotes	in
T2429	13673-13679	NN	denotes	XpdTTD
T2431	13679-13680	HYPH	denotes	/
T2430	13680-13683	NN	denotes	TTD
T2432	13684-13688	NNS	denotes	mice
T2433	13689-13690	-LRB-	denotes	[
T2434	13690-13692	CD	denotes	15
T2435	13692-13693	-RRB-	denotes	]
T2436	13694-13698	VBD	denotes	were
T2437	13699-13703	RB	denotes	both
T2438	13704-13713	RB	denotes	partially
T2413	13714-13721	VBN	denotes	rescued
T2439	13722-13724	IN	denotes	in
T2440	13725-13733	JJ	denotes	compound
T2442	13734-13746	JJ	denotes	heterozygous
T2443	13747-13753	NN	denotes	XpdTTD
T2445	13753-13754	HYPH	denotes	/
T2444	13754-13759	NN	denotes	†XPCS
T2441	13760-13764	NNS	denotes	mice
T2446	13765-13766	-LRB-	denotes	(
T2448	13766-13772	NN	denotes	Figure
T2447	13773-13775	NN	denotes	2D
T2449	13776-13779	CC	denotes	and
T2450	13780-13782	NN	denotes	2E
T2451	13782-13783	-RRB-	denotes	)
T2452	13783-13784	.	denotes	.
T2575	13806-13814	NNS	denotes	Features
T2576	13815-13817	IN	denotes	in
T2577	13818-13821	NN	denotes	TTD
T2578	13822-13826	NNS	denotes	Mice
T2579	13827-13829	IN	denotes	by
T2580	13830-13840	JJ	denotes	Homozygous
T2582	13841-13847	JJ	denotes	Lethal
T2583	13848-13851	NN	denotes	Xpd
T2581	13852-13859	NNS	denotes	Alleles
T2584	13859-14093	sentence	denotes	Because patients with TTD, XPCS, and CS (but not XP) and the corresponding mouse models share similar accelerated progeroid symptoms [12,13,15,23], we next addressed ageing-related parameters in compound heterozygous mice (Figure 3).
T2585	13860-13867	IN	denotes	Because
T2587	13868-13876	NNS	denotes	patients
T2588	13877-13881	IN	denotes	with
T2589	13882-13885	NN	denotes	TTD
T2590	13885-13887	,	denotes	,
T2591	13887-13891	NN	denotes	XPCS
T2592	13891-13893	,	denotes	,
T2593	13893-13896	CC	denotes	and
T2594	13897-13899	NN	denotes	CS
T2595	13900-13901	-LRB-	denotes	(
T2596	13901-13904	CC	denotes	but
T2597	13905-13908	RB	denotes	not
T2598	13909-13911	NN	denotes	XP
T2599	13911-13912	-RRB-	denotes	)
T2600	13913-13916	CC	denotes	and
T2601	13917-13920	DT	denotes	the
T2603	13921-13934	VBG	denotes	corresponding
T2604	13935-13940	NN	denotes	mouse
T2602	13941-13947	NNS	denotes	models
T2586	13948-13953	VBP	denotes	share
T2606	13954-13961	JJ	denotes	similar
T2608	13962-13973	VBN	denotes	accelerated
T2609	13974-13983	NN	denotes	progeroid
T2607	13984-13992	NNS	denotes	symptoms
T2610	13993-13994	-LRB-	denotes	[
T2612	13994-13996	CD	denotes	12
T2613	13996-13997	,	denotes	,
T2614	13997-13999	CD	denotes	13
T2615	13999-14000	,	denotes	,
T2616	14000-14002	CD	denotes	15
T2617	14002-14003	,	denotes	,
T2611	14003-14005	CD	denotes	23
T2618	14005-14006	-RRB-	denotes	]
T2619	14006-14008	,	denotes	,
T2620	14008-14010	PRP	denotes	we
T2621	14011-14015	RB	denotes	next
T2605	14016-14025	VBD	denotes	addressed
T2622	14026-14032	JJ	denotes	ageing
T2624	14032-14033	HYPH	denotes	-
T2623	14033-14040	JJ	denotes	related
T2625	14041-14051	NNS	denotes	parameters
T2626	14052-14054	IN	denotes	in
T2627	14055-14063	JJ	denotes	compound
T2629	14064-14076	JJ	denotes	heterozygous
T2628	14077-14081	NNS	denotes	mice
T2630	14082-14083	-LRB-	denotes	(
T2631	14083-14089	NN	denotes	Figure
T2632	14090-14091	CD	denotes	3
T2633	14091-14092	-RRB-	denotes	)
T2634	14092-14093	.	denotes	.
T2635	14093-14356	sentence	denotes	Whereas XpdTTD/TTD animals show reduced bone mineral density as an indication of the early onset of osteoporosis before ~14 mo of age [15], tail vertebrae from compound heterozygous XpdTTD/†XPCS mice were comparable to wt even at 20 mo of age (Figure 3B and 3C).
T2636	14094-14101	IN	denotes	Whereas
T2638	14102-14108	NN	denotes	XpdTTD
T2640	14108-14109	HYPH	denotes	/
T2639	14109-14112	NN	denotes	TTD
T2641	14113-14120	NNS	denotes	animals
T2637	14121-14125	VBP	denotes	show
T2643	14126-14133	VBN	denotes	reduced
T2645	14134-14138	NN	denotes	bone
T2646	14139-14146	NN	denotes	mineral
T2644	14147-14154	NN	denotes	density
T2647	14155-14157	IN	denotes	as
T2648	14158-14160	DT	denotes	an
T2649	14161-14171	NN	denotes	indication
T2650	14172-14174	IN	denotes	of
T2651	14175-14178	DT	denotes	the
T2653	14179-14184	JJ	denotes	early
T2652	14185-14190	NN	denotes	onset
T2654	14191-14193	IN	denotes	of
T2655	14194-14206	NN	denotes	osteoporosis
T2656	14207-14213	IN	denotes	before
T2657	14214-14215	SYM	denotes	~
T2658	14215-14217	CD	denotes	14
T2659	14218-14220	NNS	denotes	mo
T2660	14221-14223	IN	denotes	of
T2661	14224-14227	NN	denotes	age
T2662	14228-14229	-LRB-	denotes	[
T2663	14229-14231	CD	denotes	15
T2664	14231-14232	-RRB-	denotes	]
T2665	14232-14234	,	denotes	,
T2666	14234-14238	NN	denotes	tail
T2667	14239-14248	NNS	denotes	vertebrae
T2668	14249-14253	IN	denotes	from
T2669	14254-14262	NN	denotes	compound
T2671	14263-14275	JJ	denotes	heterozygous
T2672	14276-14282	NN	denotes	XpdTTD
T2674	14282-14283	HYPH	denotes	/
T2673	14283-14288	NN	denotes	†XPCS
T2670	14289-14293	NNS	denotes	mice
T2642	14294-14298	VBD	denotes	were
T2675	14299-14309	JJ	denotes	comparable
T2676	14310-14312	IN	denotes	to
T2677	14313-14315	NN	denotes	wt
T2678	14316-14320	RB	denotes	even
T2679	14321-14323	IN	denotes	at
T2680	14324-14326	CD	denotes	20
T2681	14327-14329	NNS	denotes	mo
T2682	14330-14332	IN	denotes	of
T2683	14333-14336	NN	denotes	age
T2684	14337-14338	-LRB-	denotes	(
T2686	14338-14344	NN	denotes	Figure
T2685	14345-14347	NN	denotes	3B
T2687	14348-14351	CC	denotes	and
T2688	14352-14354	NN	denotes	3C
T2689	14354-14355	-RRB-	denotes	)
T2690	14355-14356	.	denotes	.
T2691	14356-14528	sentence	denotes	Furthermore, whereas XpdTTD/TTD mice developed kyphosis earlier than wt animals (onset ~3 mo versus 12–20 mo), compound heterozygous XpdTTD/†XPCS mice did not (Figure 3B).
T2692	14357-14368	RB	denotes	Furthermore
T2694	14368-14370	,	denotes	,
T2695	14370-14377	IN	denotes	whereas
T2697	14378-14384	NN	denotes	XpdTTD
T2699	14384-14385	HYPH	denotes	/
T2698	14385-14388	NN	denotes	TTD
T2700	14389-14393	NNS	denotes	mice
T2696	14394-14403	VBD	denotes	developed
T2701	14404-14412	NN	denotes	kyphosis
T2702	14413-14420	RBR	denotes	earlier
T2703	14421-14425	IN	denotes	than
T2704	14426-14428	NN	denotes	wt
T2705	14429-14436	NNS	denotes	animals
T2706	14437-14438	-LRB-	denotes	(
T2707	14438-14443	NN	denotes	onset
T2708	14444-14445	SYM	denotes	~
T2709	14445-14446	CD	denotes	3
T2710	14447-14449	NNS	denotes	mo
T2711	14450-14456	CC	denotes	versus
T2712	14457-14459	CD	denotes	12
T2714	14459-14460	SYM	denotes	–
T2713	14460-14462	CD	denotes	20
T2715	14463-14465	NNS	denotes	mo
T2716	14465-14466	-RRB-	denotes	)
T2717	14466-14468	,	denotes	,
T2718	14468-14476	JJ	denotes	compound
T2720	14477-14489	JJ	denotes	heterozygous
T2721	14490-14496	NN	denotes	XpdTTD
T2723	14496-14497	HYPH	denotes	/
T2722	14497-14502	NN	denotes	†XPCS
T2719	14503-14507	NNS	denotes	mice
T2724	14508-14511	VBD	denotes	did
T2725	14512-14515	RB	denotes	not
T2726	14516-14517	-LRB-	denotes	(
T2727	14517-14523	NN	denotes	Figure
T2693	14524-14526	NN	denotes	3B
T2728	14526-14527	-RRB-	denotes	)
T2729	14527-14528	.	denotes	.
T2730	14528-14740	sentence	denotes	Overall appearance and body weight curves revealed that TTD-associated age-related premature cachexia and lack of general fitness were fully rescued in compound heterozygous XpdTTD/†XPCS mice (Figure 3A and 3D).
T2731	14529-14536	JJ	denotes	Overall
T2732	14537-14547	NN	denotes	appearance
T2734	14548-14551	CC	denotes	and
T2735	14552-14556	NN	denotes	body
T2736	14557-14563	NN	denotes	weight
T2737	14564-14570	NNS	denotes	curves
T2733	14571-14579	VBD	denotes	revealed
T2738	14580-14584	IN	denotes	that
T2740	14585-14588	NN	denotes	TTD
T2742	14588-14589	HYPH	denotes	-
T2741	14589-14599	JJ	denotes	associated
T2744	14600-14603	NN	denotes	age
T2746	14603-14604	HYPH	denotes	-
T2745	14604-14611	JJ	denotes	related
T2747	14612-14621	JJ	denotes	premature
T2743	14622-14630	NN	denotes	cachexia
T2748	14631-14634	CC	denotes	and
T2749	14635-14639	NN	denotes	lack
T2750	14640-14642	IN	denotes	of
T2751	14643-14650	JJ	denotes	general
T2752	14651-14658	NN	denotes	fitness
T2753	14659-14663	VBD	denotes	were
T2754	14664-14669	RB	denotes	fully
T2739	14670-14677	VBN	denotes	rescued
T2755	14678-14680	IN	denotes	in
T2756	14681-14689	JJ	denotes	compound
T2758	14690-14702	JJ	denotes	heterozygous
T2759	14703-14709	NN	denotes	XpdTTD
T2761	14709-14710	HYPH	denotes	/
T2760	14710-14715	NN	denotes	†XPCS
T2757	14716-14720	NNS	denotes	mice
T2762	14721-14722	-LRB-	denotes	(
T2764	14722-14728	NN	denotes	Figure
T2763	14729-14731	NN	denotes	3A
T2765	14732-14735	CC	denotes	and
T2766	14736-14738	NN	denotes	3D
T2767	14738-14739	-RRB-	denotes	)
T2768	14739-14740	.	denotes	.
T2769	14740-14841	sentence	denotes	Finally, the life span of compound heterozygotes was extended relative to XpdTTD/TTD mice (Table 2).
T2770	14741-14748	RB	denotes	Finally
T2772	14748-14750	,	denotes	,
T2773	14750-14753	DT	denotes	the
T2775	14754-14758	NN	denotes	life
T2774	14759-14763	NN	denotes	span
T2776	14764-14766	IN	denotes	of
T2777	14767-14775	JJ	denotes	compound
T2778	14776-14789	NNS	denotes	heterozygotes
T2779	14790-14793	VBD	denotes	was
T2771	14794-14802	VBN	denotes	extended
T2780	14803-14811	JJ	denotes	relative
T2781	14812-14814	IN	denotes	to
T2782	14815-14821	NN	denotes	XpdTTD
T2784	14821-14822	HYPH	denotes	/
T2783	14822-14825	NN	denotes	TTD
T2785	14826-14830	NNS	denotes	mice
T2786	14831-14832	-LRB-	denotes	(
T2787	14832-14837	NN	denotes	Table
T2788	14838-14839	CD	denotes	2
T2789	14839-14840	-RRB-	denotes	)
T2790	14840-14841	.	denotes	.
T2791	14841-16451	sentence	denotes	Figure 3 Rescue of TTD-Associated Segmental Progeroid Features in Compound Heterozygous Xpd TTD/†XPCS Mice (A) Photographs of 20-mo-old wt, compound heterozygous XpdTTD/†XPCS, and homozygous XpdTTD/TTD mice. Note the extreme cachexia (lack of subcutaneous fat) in the XpdTTD/TTD mouse and the absence of this phenotype in wt and XpdTTD/†XPCS mice. (B) Radiographs of 20-mo-old male wt, XpdTTD/†XPCS, and XpdTTD/TTD mice. Ageing XpdTTD/TTD mice develop kyphosis (curvature of the spinal column) and reduction of bone mineral density as shown in the 6–8 segment of the tail vertebrae counted from the pelvis (see close-up at right). Note the absence of these features in the XpdTTD / † XPCS mouse. (C) Quantification of relative bone mineral density of tail vertebrae from 20-mo-old male wt (n = 3), XpdTTD/†XPCS (n = 4), and XpdTTD/TTD (n = 3) mice. The p-values indicate the significance of the difference relative to XpdTTD/TTD. Error bars indicate SEM. (D) Body weight curves as a function of time. Note that the age-dependent cachexia observed in XpdTTD/TTD mice was rescued in both male and female XpdTTD / †XPCS mice. Significant differences between wt and XpdTTD/TTD but not between wt and XpdTTD/†XPCS mice were observed at 9 and 18 mo of age as indicated by asterisks. Error bars indicate SEM. Table 2 Pleiotropic Xpd Biallelic Effects in Mice and Cells To determine whether the homozygous lethal Xpd†XPCS allele was unique in its ability to ameliorate symptoms associated with the XpdTTD allele, we generated compound heterozygous XpdTTD/†XP mice by crossing the corresponding heterozygous animals.
T8041	14852-14858	NN	denotes	Rescue
T8042	14859-14861	IN	denotes	of
T8043	14862-14865	NN	denotes	TTD
T8045	14865-14866	HYPH	denotes	-
T8044	14866-14876	JJ	denotes	Associated
T8047	14877-14886	JJ	denotes	Segmental
T8048	14887-14896	JJ	denotes	Progeroid
T8046	14897-14905	NNS	denotes	Features
T8049	14906-14908	IN	denotes	in
T8050	14909-14917	JJ	denotes	Compound
T8052	14918-14930	JJ	denotes	Heterozygous
T8053	14931-14938	NN	denotes	Xpd TTD
T8055	14938-14939	HYPH	denotes	/
T8054	14939-14944	NN	denotes	†XPCS
T8051	14945-14949	NNS	denotes	Mice
T8056	14949-15050	sentence	denotes	(A) Photographs of 20-mo-old wt, compound heterozygous XpdTTD/†XPCS, and homozygous XpdTTD/TTD mice.
T8057	14950-14951	-LRB-	denotes	(
T8058	14951-14952	LS	denotes	A
T8060	14952-14953	-RRB-	denotes	)
T8059	14954-14965	NNS	denotes	Photographs
T8061	14966-14968	IN	denotes	of
T8062	14969-14971	CD	denotes	20
T8064	14971-14972	HYPH	denotes	-
T8063	14972-14974	NN	denotes	mo
T8066	14974-14975	HYPH	denotes	-
T8065	14975-14978	JJ	denotes	old
T8068	14979-14981	NN	denotes	wt
T8069	14981-14983	,	denotes	,
T8070	14983-14991	JJ	denotes	compound
T8072	14992-15004	JJ	denotes	heterozygous
T8073	15005-15011	NN	denotes	XpdTTD
T8074	15011-15012	HYPH	denotes	/
T8071	15012-15017	NN	denotes	†XPCS
T8075	15017-15019	,	denotes	,
T8076	15019-15022	CC	denotes	and
T8077	15023-15033	JJ	denotes	homozygous
T8079	15034-15040	NN	denotes	XpdTTD
T8080	15040-15041	HYPH	denotes	/
T8078	15041-15044	NN	denotes	TTD
T8067	15045-15049	NNS	denotes	mice
T8081	15049-15050	.	denotes	.
T8082	15050-15190	sentence	denotes	Note the extreme cachexia (lack of subcutaneous fat) in the XpdTTD/TTD mouse and the absence of this phenotype in wt and XpdTTD/†XPCS mice.
T8083	15051-15055	VB	denotes	Note
T8084	15056-15059	DT	denotes	the
T8086	15060-15067	JJ	denotes	extreme
T8085	15068-15076	NN	denotes	cachexia
T8087	15077-15078	-LRB-	denotes	(
T8088	15078-15082	NN	denotes	lack
T8089	15083-15085	IN	denotes	of
T8090	15086-15098	JJ	denotes	subcutaneous
T8091	15099-15102	NN	denotes	fat
T8092	15102-15103	-RRB-	denotes	)
T8093	15104-15106	IN	denotes	in
T8094	15107-15110	DT	denotes	the
T8096	15111-15117	NN	denotes	XpdTTD
T8098	15117-15118	HYPH	denotes	/
T8097	15118-15121	NN	denotes	TTD
T8095	15122-15127	NN	denotes	mouse
T8099	15128-15131	CC	denotes	and
T8100	15132-15135	DT	denotes	the
T8101	15136-15143	NN	denotes	absence
T8102	15144-15146	IN	denotes	of
T8103	15147-15151	DT	denotes	this
T8104	15152-15161	NN	denotes	phenotype
T8105	15162-15164	IN	denotes	in
T8106	15165-15167	NN	denotes	wt
T8108	15168-15171	CC	denotes	and
T8109	15172-15178	NN	denotes	XpdTTD
T8111	15178-15179	HYPH	denotes	/
T8110	15179-15184	NN	denotes	†XPCS
T8107	15185-15189	NNS	denotes	mice
T8112	15189-15190	.	denotes	.
T8113	15190-15263	sentence	denotes	(B) Radiographs of 20-mo-old male wt, XpdTTD/†XPCS, and XpdTTD/TTD mice.
T8114	15191-15192	-LRB-	denotes	(
T8115	15192-15193	LS	denotes	B
T8117	15193-15194	-RRB-	denotes	)
T8116	15195-15206	NNS	denotes	Radiographs
T8118	15207-15209	IN	denotes	of
T8119	15210-15212	CD	denotes	20
T8121	15212-15213	HYPH	denotes	-
T8120	15213-15215	NN	denotes	mo
T8123	15215-15216	HYPH	denotes	-
T8122	15216-15219	JJ	denotes	old
T8125	15220-15224	JJ	denotes	male
T8126	15225-15227	NN	denotes	wt
T8127	15227-15229	,	denotes	,
T8128	15229-15235	NN	denotes	XpdTTD
T8130	15235-15236	HYPH	denotes	/
T8129	15236-15241	NN	denotes	†XPCS
T8131	15241-15243	,	denotes	,
T8132	15243-15246	CC	denotes	and
T8133	15247-15253	NN	denotes	XpdTTD
T8135	15253-15254	HYPH	denotes	/
T8134	15254-15257	NN	denotes	TTD
T8124	15258-15262	NNS	denotes	mice
T8136	15262-15263	.	denotes	.
T8137	15263-15473	sentence	denotes	Ageing XpdTTD/TTD mice develop kyphosis (curvature of the spinal column) and reduction of bone mineral density as shown in the 6–8 segment of the tail vertebrae counted from the pelvis (see close-up at right).
T8138	15264-15270	VBG	denotes	Ageing
T8140	15271-15277	NN	denotes	XpdTTD
T8142	15277-15278	HYPH	denotes	/
T8141	15278-15281	NN	denotes	TTD
T8139	15282-15286	NNS	denotes	mice
T8143	15287-15294	VBP	denotes	develop
T8144	15295-15303	NN	denotes	kyphosis
T8145	15304-15305	-LRB-	denotes	(
T8146	15305-15314	NN	denotes	curvature
T8147	15315-15317	IN	denotes	of
T8148	15318-15321	DT	denotes	the
T8150	15322-15328	JJ	denotes	spinal
T8149	15329-15335	NN	denotes	column
T8151	15335-15336	-RRB-	denotes	)
T8152	15337-15340	CC	denotes	and
T8153	15341-15350	NN	denotes	reduction
T8154	15351-15353	IN	denotes	of
T8155	15354-15358	NN	denotes	bone
T8156	15359-15366	NN	denotes	mineral
T8157	15367-15374	NN	denotes	density
T8158	15375-15377	IN	denotes	as
T8159	15378-15383	VBN	denotes	shown
T8160	15384-15386	IN	denotes	in
T8161	15387-15390	DT	denotes	the
T8163	15391-15392	CD	denotes	6
T8165	15392-15393	SYM	denotes	–
T8164	15393-15394	CD	denotes	8
T8162	15395-15402	NN	denotes	segment
T8166	15403-15405	IN	denotes	of
T8167	15406-15409	DT	denotes	the
T8169	15410-15414	NN	denotes	tail
T8168	15415-15424	NNS	denotes	vertebrae
T8170	15425-15432	VBN	denotes	counted
T8171	15433-15437	IN	denotes	from
T8172	15438-15441	DT	denotes	the
T8173	15442-15448	NN	denotes	pelvis
T8174	15449-15450	-LRB-	denotes	(
T8175	15450-15453	VB	denotes	see
T8176	15454-15459	JJ	denotes	close
T8177	15459-15460	HYPH	denotes	-
T8178	15460-15462	RP	denotes	up
T8179	15463-15465	IN	denotes	at
T8180	15466-15471	NN	denotes	right
T8181	15471-15472	-RRB-	denotes	)
T8182	15472-15473	.	denotes	.
T8183	15473-15538	sentence	denotes	Note the absence of these features in the XpdTTD / † XPCS mouse.
T8184	15474-15478	VB	denotes	Note
T8185	15479-15482	DT	denotes	the
T8186	15483-15490	NN	denotes	absence
T8187	15491-15493	IN	denotes	of
T8188	15494-15499	DT	denotes	these
T8189	15500-15508	NNS	denotes	features
T8190	15509-15511	IN	denotes	in
T8191	15512-15515	DT	denotes	the
T8193	15516-15523	NN	denotes	XpdTTD
T8195	15523-15524	HYPH	denotes	/
T8194	15524-15531	NN	denotes	† XPCS
T8192	15532-15537	NN	denotes	mouse
T8196	15537-15538	.	denotes	.
T8197	15538-15691	sentence	denotes	(C) Quantification of relative bone mineral density of tail vertebrae from 20-mo-old male wt (n = 3), XpdTTD/†XPCS (n = 4), and XpdTTD/TTD (n = 3) mice.
T8198	15539-15540	-LRB-	denotes	(
T8199	15540-15541	LS	denotes	C
T8201	15541-15542	-RRB-	denotes	)
T8200	15543-15557	NN	denotes	Quantification
T8202	15558-15560	IN	denotes	of
T8203	15561-15569	JJ	denotes	relative
T8205	15570-15574	NN	denotes	bone
T8206	15575-15582	NN	denotes	mineral
T8204	15583-15590	NN	denotes	density
T8207	15591-15593	IN	denotes	of
T8208	15594-15598	NN	denotes	tail
T8209	15599-15608	NNS	denotes	vertebrae
T8210	15609-15613	IN	denotes	from
T8211	15614-15616	CD	denotes	20
T8213	15616-15617	HYPH	denotes	-
T8212	15617-15619	NN	denotes	mo
T8215	15619-15620	HYPH	denotes	-
T8214	15620-15623	JJ	denotes	old
T8217	15624-15628	JJ	denotes	male
T8218	15629-15631	NN	denotes	wt
T8219	15632-15633	-LRB-	denotes	(
T8221	15633-15634	NN	denotes	n
T8222	15635-15636	SYM	denotes	=
T8220	15637-15638	CD	denotes	3
T8223	15638-15639	-RRB-	denotes	)
T8224	15639-15641	,	denotes	,
T8225	15641-15647	NN	denotes	XpdTTD
T8227	15647-15648	HYPH	denotes	/
T8226	15648-15653	NN	denotes	†XPCS
T8228	15654-15655	-LRB-	denotes	(
T8230	15655-15656	NN	denotes	n
T8231	15657-15658	SYM	denotes	=
T8229	15659-15660	CD	denotes	4
T8232	15660-15661	-RRB-	denotes	)
T8233	15661-15663	,	denotes	,
T8234	15663-15666	CC	denotes	and
T8235	15667-15673	NN	denotes	XpdTTD
T8237	15673-15674	HYPH	denotes	/
T8236	15674-15677	NN	denotes	TTD
T8238	15678-15679	-LRB-	denotes	(
T8240	15679-15680	NN	denotes	n
T8241	15681-15682	SYM	denotes	=
T8239	15683-15684	CD	denotes	3
T8242	15684-15685	-RRB-	denotes	)
T8216	15686-15690	NNS	denotes	mice
T8243	15690-15691	.	denotes	.
T8244	15691-15772	sentence	denotes	The p-values indicate the significance of the difference relative to XpdTTD/TTD.
T8245	15692-15695	DT	denotes	The
T8247	15696-15697	NN	denotes	p
T8248	15697-15698	HYPH	denotes	-
T8246	15698-15704	NNS	denotes	values
T8249	15705-15713	VBP	denotes	indicate
T8250	15714-15717	DT	denotes	the
T8251	15718-15730	NN	denotes	significance
T8252	15731-15733	IN	denotes	of
T8253	15734-15737	DT	denotes	the
T8254	15738-15748	NN	denotes	difference
T8255	15749-15757	JJ	denotes	relative
T8256	15758-15760	IN	denotes	to
T8257	15761-15767	NN	denotes	XpdTTD
T8259	15767-15768	HYPH	denotes	/
T8258	15768-15771	NN	denotes	TTD
T8260	15771-15772	.	denotes	.
T8261	15772-15797	sentence	denotes	Error bars indicate SEM.
T8262	15773-15778	NN	denotes	Error
T8263	15779-15783	NNS	denotes	bars
T8264	15784-15792	VBP	denotes	indicate
T8265	15793-15796	NN	denotes	SEM
T8266	15796-15797	.	denotes	.
T8267	15797-15843	sentence	denotes	(D) Body weight curves as a function of time.
T8268	15798-15799	-LRB-	denotes	(
T8269	15799-15800	LS	denotes	D
T8271	15800-15801	-RRB-	denotes	)
T8272	15802-15806	NN	denotes	Body
T8273	15807-15813	NN	denotes	weight
T8270	15814-15820	NNS	denotes	curves
T8274	15821-15823	IN	denotes	as
T8275	15824-15825	DT	denotes	a
T8276	15826-15834	NN	denotes	function
T8277	15835-15837	IN	denotes	of
T8278	15838-15842	NN	denotes	time
T8279	15842-15843	.	denotes	.
T8280	15843-15965	sentence	denotes	Note that the age-dependent cachexia observed in XpdTTD/TTD mice was rescued in both male and female XpdTTD / †XPCS mice.
T8281	15844-15848	VB	denotes	Note
T8282	15849-15853	IN	denotes	that
T8284	15854-15857	DT	denotes	the
T8286	15858-15861	NN	denotes	age
T8288	15861-15862	HYPH	denotes	-
T8287	15862-15871	JJ	denotes	dependent
T8285	15872-15880	NN	denotes	cachexia
T8289	15881-15889	VBN	denotes	observed
T8290	15890-15892	IN	denotes	in
T8291	15893-15899	NN	denotes	XpdTTD
T8293	15899-15900	HYPH	denotes	/
T8292	15900-15903	NN	denotes	TTD
T8294	15904-15908	NNS	denotes	mice
T8295	15909-15912	VBD	denotes	was
T8283	15913-15920	VBN	denotes	rescued
T8296	15921-15923	IN	denotes	in
T8297	15924-15928	CC	denotes	both
T8298	15929-15933	JJ	denotes	male
T8300	15934-15937	CC	denotes	and
T8301	15938-15944	JJ	denotes	female
T8302	15945-15952	NN	denotes	XpdTTD
T8304	15952-15953	HYPH	denotes	/
T8303	15953-15959	NN	denotes	†XPCS
T8299	15960-15964	NNS	denotes	mice
T8305	15964-15965	.	denotes	.
T8306	15965-16119	sentence	denotes	Significant differences between wt and XpdTTD/TTD but not between wt and XpdTTD/†XPCS mice were observed at 9 and 18 mo of age as indicated by asterisks.
T8307	15966-15977	JJ	denotes	Significant
T8308	15978-15989	NNS	denotes	differences
T8310	15990-15997	IN	denotes	between
T8311	15998-16000	NN	denotes	wt
T8312	16001-16004	CC	denotes	and
T8313	16005-16011	NN	denotes	XpdTTD
T8315	16011-16012	HYPH	denotes	/
T8314	16012-16015	NN	denotes	TTD
T8316	16016-16019	CC	denotes	but
T8317	16020-16023	RB	denotes	not
T8318	16024-16031	IN	denotes	between
T8319	16032-16034	NN	denotes	wt
T8321	16035-16038	CC	denotes	and
T8322	16039-16045	NN	denotes	XpdTTD
T8324	16045-16046	HYPH	denotes	/
T8323	16046-16051	NN	denotes	†XPCS
T8320	16052-16056	NNS	denotes	mice
T8325	16057-16061	VBD	denotes	were
T8309	16062-16070	VBN	denotes	observed
T8326	16071-16073	IN	denotes	at
T8327	16074-16075	CD	denotes	9
T8329	16076-16079	CC	denotes	and
T8330	16080-16082	CD	denotes	18
T8328	16083-16085	NNS	denotes	mo
T8331	16086-16088	IN	denotes	of
T8332	16089-16092	NN	denotes	age
T8333	16093-16095	IN	denotes	as
T8334	16096-16105	VBN	denotes	indicated
T8335	16106-16108	IN	denotes	by
T8336	16109-16118	NNS	denotes	asterisks
T8337	16118-16119	.	denotes	.
T8338	16119-16144	sentence	denotes	Error bars indicate SEM.
T8339	16120-16125	NN	denotes	Error
T8340	16126-16130	NNS	denotes	bars
T8341	16131-16139	VBP	denotes	indicate
T8342	16140-16143	NN	denotes	SEM
T8343	16143-16144	.	denotes	.
T9241	16154-16165	JJ	denotes	Pleiotropic
T9243	16166-16169	NN	denotes	Xpd
T9244	16170-16179	JJ	denotes	Biallelic
T9242	16180-16187	NNS	denotes	Effects
T9245	16188-16190	IN	denotes	in
T9246	16191-16195	NNS	denotes	Mice
T9247	16196-16199	CC	denotes	and
T9248	16200-16205	NNS	denotes	Cells
T2792	16206-16208	TO	denotes	To
T2793	16209-16218	VB	denotes	determine
T2795	16219-16226	IN	denotes	whether
T2797	16227-16230	DT	denotes	the
T2799	16231-16241	JJ	denotes	homozygous
T2800	16242-16248	JJ	denotes	lethal
T2801	16249-16257	NN	denotes	Xpd†XPCS
T2798	16258-16264	NN	denotes	allele
T2796	16265-16268	VBD	denotes	was
T2802	16269-16275	JJ	denotes	unique
T2803	16276-16278	IN	denotes	in
T2804	16279-16282	PRP$	denotes	its
T2805	16283-16290	NN	denotes	ability
T2806	16291-16293	TO	denotes	to
T2807	16294-16304	VB	denotes	ameliorate
T2808	16305-16313	NNS	denotes	symptoms
T2809	16314-16324	VBN	denotes	associated
T2810	16325-16329	IN	denotes	with
T2811	16330-16333	DT	denotes	the
T2813	16334-16340	NN	denotes	XpdTTD
T2812	16341-16347	NN	denotes	allele
T2814	16347-16349	,	denotes	,
T2815	16349-16351	PRP	denotes	we
T2794	16352-16361	VBD	denotes	generated
T2816	16362-16370	NN	denotes	compound
T2818	16371-16383	JJ	denotes	heterozygous
T2819	16384-16390	NN	denotes	XpdTTD
T2821	16390-16391	HYPH	denotes	/
T2820	16391-16394	NN	denotes	†XP
T2817	16395-16399	NNS	denotes	mice
T2822	16400-16402	IN	denotes	by
T2823	16403-16411	VBG	denotes	crossing
T2824	16412-16415	DT	denotes	the
T2826	16416-16429	VBG	denotes	corresponding
T2827	16430-16442	JJ	denotes	heterozygous
T2825	16443-16450	NNS	denotes	animals
T2828	16450-16451	.	denotes	.
T2829	16451-16897	sentence	denotes	Similar to the Xpd †XPCS allele, the homozygous lethal Xpd †XP allele rescued cutaneous symptoms including hair loss (except locally during the first round; unpublished data), reduced cysteine content (cysteine index 9.3 ± 0.9 standard deviation [87% of wt], p = 0.01 versus TTD), ageing-associated premature cachexia (males and females were 36.1 ± 6.4 g [93% of wt] and 39.2 ± 3.2 g [116% of wt], respectively), and reduced life span (Table 2).
T2830	16452-16459	JJ	denotes	Similar
T2832	16460-16462	IN	denotes	to
T2833	16463-16466	DT	denotes	the
T2835	16467-16476	NN	denotes	Xpd †XPCS
T2834	16477-16483	NN	denotes	allele
T2836	16483-16485	,	denotes	,
T2837	16485-16488	DT	denotes	the
T2839	16489-16499	JJ	denotes	homozygous
T2840	16500-16506	JJ	denotes	lethal
T2841	16507-16514	NN	denotes	Xpd †XP
T2838	16515-16521	NN	denotes	allele
T2831	16522-16529	VBD	denotes	rescued
T2842	16530-16539	JJ	denotes	cutaneous
T2843	16540-16548	NNS	denotes	symptoms
T2844	16549-16558	VBG	denotes	including
T2845	16559-16563	NN	denotes	hair
T2846	16564-16568	NN	denotes	loss
T2847	16569-16570	-LRB-	denotes	(
T2849	16570-16576	IN	denotes	except
T2850	16577-16584	RB	denotes	locally
T2851	16585-16591	IN	denotes	during
T2852	16592-16595	DT	denotes	the
T2854	16596-16601	JJ	denotes	first
T2853	16602-16607	NN	denotes	round
T2855	16607-16608	:	denotes	;
T2856	16609-16620	JJ	denotes	unpublished
T2848	16621-16625	NNS	denotes	data
T2857	16625-16626	-RRB-	denotes	)
T2858	16626-16628	,	denotes	,
T2859	16628-16635	VBN	denotes	reduced
T2861	16636-16644	NN	denotes	cysteine
T2860	16645-16652	NN	denotes	content
T2862	16653-16654	-LRB-	denotes	(
T2864	16654-16662	NN	denotes	cysteine
T2863	16663-16668	NN	denotes	index
T2865	16669-16672	CD	denotes	9.3
T2866	16673-16674	SYM	denotes	±
T2867	16675-16678	CD	denotes	0.9
T2869	16679-16687	JJ	denotes	standard
T2868	16688-16697	NN	denotes	deviation
T2870	16698-16699	-LRB-	denotes	[
T2872	16699-16701	CD	denotes	87
T2871	16701-16702	NN	denotes	%
T2873	16703-16705	IN	denotes	of
T2874	16706-16708	NN	denotes	wt
T2875	16708-16709	-RRB-	denotes	]
T2876	16709-16711	,	denotes	,
T2877	16711-16712	NN	denotes	p
T2879	16713-16714	SYM	denotes	=
T2880	16715-16719	CD	denotes	0.01
T2881	16720-16726	CC	denotes	versus
T2878	16727-16730	NN	denotes	TTD
T2882	16730-16731	-RRB-	denotes	)
T2883	16731-16733	,	denotes	,
T2884	16733-16739	NN	denotes	ageing
T2886	16739-16740	HYPH	denotes	-
T2885	16740-16750	VBN	denotes	associated
T2888	16751-16760	JJ	denotes	premature
T2887	16761-16769	NN	denotes	cachexia
T2889	16770-16771	-LRB-	denotes	(
T2891	16771-16776	NNS	denotes	males
T2892	16777-16780	CC	denotes	and
T2893	16781-16788	NNS	denotes	females
T2890	16789-16793	VBD	denotes	were
T2894	16794-16798	CD	denotes	36.1
T2896	16799-16800	SYM	denotes	±
T2895	16801-16804	CD	denotes	6.4
T2897	16805-16806	NNS	denotes	g
T2898	16807-16808	-LRB-	denotes	[
T2900	16808-16810	CD	denotes	93
T2899	16810-16811	NN	denotes	%
T2901	16812-16814	IN	denotes	of
T2902	16815-16817	NN	denotes	wt
T2903	16817-16818	-RRB-	denotes	]
T2904	16819-16822	CC	denotes	and
T2905	16823-16827	CD	denotes	39.2
T2907	16828-16829	SYM	denotes	±
T2906	16830-16833	CD	denotes	3.2
T2908	16834-16835	NNS	denotes	g
T2909	16836-16837	-LRB-	denotes	[
T2911	16837-16840	CD	denotes	116
T2910	16840-16841	NN	denotes	%
T2912	16842-16844	IN	denotes	of
T2913	16845-16847	NN	denotes	wt
T2914	16847-16848	-RRB-	denotes	]
T2915	16848-16850	,	denotes	,
T2916	16850-16862	RB	denotes	respectively
T2917	16862-16863	-RRB-	denotes	)
T2918	16863-16865	,	denotes	,
T2919	16865-16868	CC	denotes	and
T2920	16869-16876	VBN	denotes	reduced
T2922	16877-16881	NN	denotes	life
T2921	16882-16886	NN	denotes	span
T2923	16887-16888	-LRB-	denotes	(
T2924	16888-16893	NN	denotes	Table
T2925	16894-16895	CD	denotes	2
T2926	16895-16896	-RRB-	denotes	)
T2927	16896-16897	.	denotes	.
T2928	16897-17106	sentence	denotes	Taken together, these data indicate that two independent alleles, which on their own are unable to support viability (Table 1), were nonetheless able to ameliorate TTD-associated phenotypes in vivo (Table 2).
T2929	16898-16903	VBN	denotes	Taken
T2931	16904-16912	RB	denotes	together
T2932	16912-16914	,	denotes	,
T2933	16914-16919	DT	denotes	these
T2934	16920-16924	NNS	denotes	data
T2930	16925-16933	VBP	denotes	indicate
T2935	16934-16938	IN	denotes	that
T2937	16939-16942	CD	denotes	two
T2939	16943-16954	JJ	denotes	independent
T2938	16955-16962	NNS	denotes	alleles
T2940	16962-16964	,	denotes	,
T2941	16964-16969	WDT	denotes	which
T2943	16970-16972	IN	denotes	on
T2944	16973-16978	PRP$	denotes	their
T2945	16979-16982	NN	denotes	own
T2942	16983-16986	VBP	denotes	are
T2946	16987-16993	JJ	denotes	unable
T2947	16994-16996	TO	denotes	to
T2948	16997-17004	VB	denotes	support
T2949	17005-17014	NN	denotes	viability
T2950	17015-17016	-LRB-	denotes	(
T2951	17016-17021	NN	denotes	Table
T2952	17022-17023	CD	denotes	1
T2953	17023-17024	-RRB-	denotes	)
T2954	17024-17026	,	denotes	,
T2936	17026-17030	VBD	denotes	were
T2955	17031-17042	RB	denotes	nonetheless
T2956	17043-17047	JJ	denotes	able
T2957	17048-17050	TO	denotes	to
T2958	17051-17061	VB	denotes	ameliorate
T2959	17062-17065	NN	denotes	TTD
T2961	17065-17066	HYPH	denotes	-
T2960	17066-17076	VBN	denotes	associated
T2962	17077-17087	NNS	denotes	phenotypes
T2963	17088-17090	FW	denotes	in
T2964	17091-17095	FW	denotes	vivo
T2965	17096-17097	-LRB-	denotes	(
T2966	17097-17102	NN	denotes	Table
T2967	17103-17104	CD	denotes	2
T2968	17104-17105	-RRB-	denotes	)
T2969	17105-17106	.	denotes	.
T3312	17108-17117	JJ	denotes	Molecular
T3313	17118-17128	NNS	denotes	Mechanisms
T3314	17129-17131	IN	denotes	of
T3315	17132-17141	JJ	denotes	Biallelic
T3316	17142-17149	NNS	denotes	Effects
T3317	17149-17448	sentence	denotes	We next turned to UV-based cellular assays including unscheduled DNA synthesis after UV irradiation (UV-UDS), recovery of RNA synthesis after UV irradiation (UV-RRS), and UV survival, which report on the NER subpathways (global genome NER and transcription-coupled NER) and total NER, respectively.
T3318	17150-17152	PRP	denotes	We
T3320	17153-17157	RB	denotes	next
T3319	17158-17164	VBD	denotes	turned
T3321	17165-17167	IN	denotes	to
T3322	17168-17170	NN	denotes	UV
T3324	17170-17171	HYPH	denotes	-
T3323	17171-17176	VBN	denotes	based
T3326	17177-17185	JJ	denotes	cellular
T3325	17186-17192	NNS	denotes	assays
T3327	17193-17202	VBG	denotes	including
T3328	17203-17214	JJ	denotes	unscheduled
T3330	17215-17218	NN	denotes	DNA
T3329	17219-17228	NN	denotes	synthesis
T3331	17229-17234	IN	denotes	after
T3332	17235-17237	NN	denotes	UV
T3333	17238-17249	NN	denotes	irradiation
T3334	17250-17251	-LRB-	denotes	(
T3336	17251-17253	NN	denotes	UV
T3337	17253-17254	HYPH	denotes	-
T3335	17254-17257	NN	denotes	UDS
T3338	17257-17258	-RRB-	denotes	)
T3339	17258-17260	,	denotes	,
T3340	17260-17268	NN	denotes	recovery
T3341	17269-17271	IN	denotes	of
T3342	17272-17275	NN	denotes	RNA
T3343	17276-17285	NN	denotes	synthesis
T3344	17286-17291	IN	denotes	after
T3345	17292-17294	NN	denotes	UV
T3346	17295-17306	NN	denotes	irradiation
T3347	17307-17308	-LRB-	denotes	(
T3349	17308-17310	NN	denotes	UV
T3350	17310-17311	HYPH	denotes	-
T3348	17311-17314	NN	denotes	RRS
T3351	17314-17315	-RRB-	denotes	)
T3352	17315-17317	,	denotes	,
T3353	17317-17320	CC	denotes	and
T3354	17321-17323	NN	denotes	UV
T3355	17324-17332	NN	denotes	survival
T3356	17332-17334	,	denotes	,
T3357	17334-17339	WDT	denotes	which
T3358	17340-17346	VBP	denotes	report
T3359	17347-17349	IN	denotes	on
T3360	17350-17353	DT	denotes	the
T3362	17354-17357	NN	denotes	NER
T3361	17358-17369	NNS	denotes	subpathways
T3363	17370-17371	-LRB-	denotes	(
T3365	17371-17377	JJ	denotes	global
T3366	17378-17384	NN	denotes	genome
T3364	17385-17388	NN	denotes	NER
T3367	17389-17392	CC	denotes	and
T3368	17393-17406	NN	denotes	transcription
T3370	17406-17407	HYPH	denotes	-
T3369	17407-17414	VBN	denotes	coupled
T3371	17415-17418	NN	denotes	NER
T3372	17418-17419	-RRB-	denotes	)
T3373	17420-17423	CC	denotes	and
T3374	17424-17429	JJ	denotes	total
T3375	17430-17433	NN	denotes	NER
T3376	17433-17435	,	denotes	,
T3377	17435-17447	RB	denotes	respectively
T3378	17447-17448	.	denotes	.
T3379	17448-17574	sentence	denotes	In none of these assays was the response to UV improved in compound heterozygotes relative to TTD homozygotes (Figure 4A–4C).
T3380	17449-17451	IN	denotes	In
T3382	17452-17456	NN	denotes	none
T3383	17457-17459	IN	denotes	of
T3384	17460-17465	DT	denotes	these
T3385	17466-17472	NNS	denotes	assays
T3386	17473-17476	VBD	denotes	was
T3387	17477-17480	DT	denotes	the
T3388	17481-17489	NN	denotes	response
T3389	17490-17492	IN	denotes	to
T3390	17493-17495	NN	denotes	UV
T3381	17496-17504	VBN	denotes	improved
T3391	17505-17507	IN	denotes	in
T3392	17508-17516	NN	denotes	compound
T3393	17517-17530	NNS	denotes	heterozygotes
T3394	17531-17539	JJ	denotes	relative
T3395	17540-17542	IN	denotes	to
T3396	17543-17546	NN	denotes	TTD
T3397	17547-17558	NNS	denotes	homozygotes
T3398	17559-17560	-LRB-	denotes	(
T3400	17560-17566	NN	denotes	Figure
T3399	17567-17569	NN	denotes	4A
T3401	17569-17570	SYM	denotes	–
T3402	17570-17572	NN	denotes	4C
T3403	17572-17573	-RRB-	denotes	)
T3404	17573-17574	.	denotes	.
T3405	17574-17920	sentence	denotes	However, unlike the in vivo TTD phenotypes described above, in which XpdTTD/TTD and XpdTTD/KO animals were indistinguishable, XpdTTD dosage effects were observed in UV survival, UV-UDS, and UV-RRS, indicating that cellular parameters as measured in fibroblasts here do not always correlate with the phenotype at the level of the intact organism.
T3406	17575-17582	RB	denotes	However
T3408	17582-17584	,	denotes	,
T3409	17584-17590	IN	denotes	unlike
T3410	17591-17594	DT	denotes	the
T3412	17595-17597	FW	denotes	in
T3413	17598-17602	FW	denotes	vivo
T3414	17603-17606	NN	denotes	TTD
T3411	17607-17617	NNS	denotes	phenotypes
T3415	17618-17627	VBN	denotes	described
T3416	17628-17633	RB	denotes	above
T3417	17633-17635	,	denotes	,
T3418	17635-17637	IN	denotes	in
T3420	17638-17643	WDT	denotes	which
T3421	17644-17650	NN	denotes	XpdTTD
T3423	17650-17651	HYPH	denotes	/
T3422	17651-17654	NN	denotes	TTD
T3425	17655-17658	CC	denotes	and
T3426	17659-17665	NN	denotes	XpdTTD
T3428	17665-17666	HYPH	denotes	/
T3427	17666-17668	NN	denotes	KO
T3424	17669-17676	NNS	denotes	animals
T3419	17677-17681	VBD	denotes	were
T3429	17682-17699	JJ	denotes	indistinguishable
T3430	17699-17701	,	denotes	,
T3431	17701-17707	NN	denotes	XpdTTD
T3433	17708-17714	NN	denotes	dosage
T3432	17715-17722	NNS	denotes	effects
T3434	17723-17727	VBD	denotes	were
T3407	17728-17736	VBN	denotes	observed
T3435	17737-17739	IN	denotes	in
T3436	17740-17742	NN	denotes	UV
T3437	17743-17751	NN	denotes	survival
T3438	17751-17753	,	denotes	,
T3439	17753-17755	NN	denotes	UV
T3441	17755-17756	HYPH	denotes	-
T3440	17756-17759	NN	denotes	UDS
T3442	17759-17761	,	denotes	,
T3443	17761-17764	CC	denotes	and
T3444	17765-17767	NN	denotes	UV
T3446	17767-17768	HYPH	denotes	-
T3445	17768-17771	NN	denotes	RRS
T3447	17771-17773	,	denotes	,
T3448	17773-17783	VBG	denotes	indicating
T3449	17784-17788	IN	denotes	that
T3451	17789-17797	JJ	denotes	cellular
T3452	17798-17808	NNS	denotes	parameters
T3453	17809-17811	IN	denotes	as
T3454	17812-17820	VBN	denotes	measured
T3455	17821-17823	IN	denotes	in
T3456	17824-17835	NNS	denotes	fibroblasts
T3457	17836-17840	RB	denotes	here
T3458	17841-17843	VBP	denotes	do
T3459	17844-17847	RB	denotes	not
T3460	17848-17854	RB	denotes	always
T3450	17855-17864	VB	denotes	correlate
T3461	17865-17869	IN	denotes	with
T3462	17870-17873	DT	denotes	the
T3463	17874-17883	NN	denotes	phenotype
T3464	17884-17886	IN	denotes	at
T3465	17887-17890	DT	denotes	the
T3466	17891-17896	NN	denotes	level
T3467	17897-17899	IN	denotes	of
T3468	17900-17903	DT	denotes	the
T3470	17904-17910	JJ	denotes	intact
T3469	17911-17919	NN	denotes	organism
T3471	17919-17920	.	denotes	.
T3472	17920-18043	sentence	denotes	XpdTTD/KO hemizygous cells were thus used as the baseline on which to compare the activity of compound heterozygous cells.
T3473	17921-17927	NN	denotes	XpdTTD
T3475	17927-17928	HYPH	denotes	/
T3474	17928-17930	NN	denotes	KO
T3477	17931-17941	JJ	denotes	hemizygous
T3476	17942-17947	NNS	denotes	cells
T3479	17948-17952	VBD	denotes	were
T3480	17953-17957	RB	denotes	thus
T3478	17958-17962	VBN	denotes	used
T3481	17963-17965	IN	denotes	as
T3482	17966-17969	DT	denotes	the
T3483	17970-17978	NN	denotes	baseline
T3484	17979-17981	IN	denotes	on
T3486	17982-17987	WDT	denotes	which
T3487	17988-17990	TO	denotes	to
T3485	17991-17998	VB	denotes	compare
T3488	17999-18002	DT	denotes	the
T3489	18003-18011	NN	denotes	activity
T3490	18012-18014	IN	denotes	of
T3491	18015-18023	NN	denotes	compound
T3493	18024-18036	JJ	denotes	heterozygous
T3492	18037-18042	NNS	denotes	cells
T3494	18042-18043	.	denotes	.
T3495	18043-18250	sentence	denotes	Relative to XpdTTD/KO hemizygote cells, UV survival was improved by the homozygous lethal Xpd†XPCS allele in XpdTTD/†XPCS compound heterozygous cells and to a lesser degree by the Xpd†XP allele (Figure 4A).
T3496	18044-18052	JJ	denotes	Relative
T3498	18053-18055	IN	denotes	to
T3499	18056-18062	NN	denotes	XpdTTD
T3501	18062-18063	HYPH	denotes	/
T3500	18063-18065	NN	denotes	KO
T3503	18066-18076	NN	denotes	hemizygote
T3502	18077-18082	NNS	denotes	cells
T3504	18082-18084	,	denotes	,
T3505	18084-18086	NN	denotes	UV
T3506	18087-18095	NN	denotes	survival
T3507	18096-18099	VBD	denotes	was
T3497	18100-18108	VBN	denotes	improved
T3508	18109-18111	IN	denotes	by
T3509	18112-18115	DT	denotes	the
T3511	18116-18126	JJ	denotes	homozygous
T3512	18127-18133	JJ	denotes	lethal
T3513	18134-18142	NN	denotes	Xpd†XPCS
T3510	18143-18149	NN	denotes	allele
T3514	18150-18152	IN	denotes	in
T3515	18153-18159	NN	denotes	XpdTTD
T3517	18159-18160	HYPH	denotes	/
T3516	18160-18165	NN	denotes	†XPCS
T3519	18166-18174	NN	denotes	compound
T3520	18175-18187	JJ	denotes	heterozygous
T3518	18188-18193	NNS	denotes	cells
T3521	18194-18197	CC	denotes	and
T3522	18198-18200	IN	denotes	to
T3524	18201-18202	DT	denotes	a
T3526	18203-18209	JJR	denotes	lesser
T3525	18210-18216	NN	denotes	degree
T3523	18217-18219	IN	denotes	by
T3527	18220-18223	DT	denotes	the
T3529	18224-18230	NN	denotes	Xpd†XP
T3528	18231-18237	NN	denotes	allele
T3530	18238-18239	-LRB-	denotes	(
T3532	18239-18245	NN	denotes	Figure
T3531	18246-18248	NN	denotes	4A
T3533	18248-18249	-RRB-	denotes	)
T3534	18249-18250	.	denotes	.
T3535	18250-18390	sentence	denotes	Because of embryonic and cellular lethality, we were unable to test UV survival associated exclusively with the Xpd†XPCS or Xpd†XP alleles.
T3536	18251-18258	IN	denotes	Because
T3538	18259-18261	IN	denotes	of
T3539	18262-18271	JJ	denotes	embryonic
T3541	18272-18275	CC	denotes	and
T3542	18276-18284	JJ	denotes	cellular
T3540	18285-18294	NN	denotes	lethality
T3543	18294-18296	,	denotes	,
T3544	18296-18298	PRP	denotes	we
T3537	18299-18303	VBD	denotes	were
T3545	18304-18310	JJ	denotes	unable
T3546	18311-18313	TO	denotes	to
T3547	18314-18318	VB	denotes	test
T3548	18319-18321	NN	denotes	UV
T3549	18322-18330	NN	denotes	survival
T3550	18331-18341	VBN	denotes	associated
T3551	18342-18353	RB	denotes	exclusively
T3552	18354-18358	IN	denotes	with
T3553	18359-18362	DT	denotes	the
T3555	18363-18371	NN	denotes	Xpd†XPCS
T3556	18372-18374	CC	denotes	or
T3557	18375-18381	NN	denotes	Xpd†XP
T3554	18382-18389	NNS	denotes	alleles
T3558	18389-18390	.	denotes	.
T3559	18390-18632	sentence	denotes	However, homozygous XPDXP (XPDR683W) and hemizygous XPDXPCS (XPDG602D) human cells are known to be highly sensitive to UV [19,25], as are cells from a homozygous viable XpdXPCS/XPCS (XPDG602D/G602D) mouse model (Figure 4A, dotted line) [23].
T3560	18391-18398	RB	denotes	However
T3562	18398-18400	,	denotes	,
T3563	18400-18410	JJ	denotes	homozygous
T3564	18411-18416	NN	denotes	XPDXP
T3566	18417-18418	-LRB-	denotes	(
T3567	18418-18426	NN	denotes	XPDR683W
T3568	18426-18427	-RRB-	denotes	)
T3569	18428-18431	CC	denotes	and
T3570	18432-18442	JJ	denotes	hemizygous
T3571	18443-18450	NN	denotes	XPDXPCS
T3572	18451-18452	-LRB-	denotes	(
T3573	18452-18460	NN	denotes	XPDG602D
T3574	18460-18461	-RRB-	denotes	)
T3575	18462-18467	JJ	denotes	human
T3565	18468-18473	NNS	denotes	cells
T3576	18474-18477	VBP	denotes	are
T3561	18478-18483	VBN	denotes	known
T3577	18484-18486	TO	denotes	to
T3578	18487-18489	VB	denotes	be
T3579	18490-18496	RB	denotes	highly
T3580	18497-18506	JJ	denotes	sensitive
T3581	18507-18509	IN	denotes	to
T3582	18510-18512	NN	denotes	UV
T3583	18513-18514	-LRB-	denotes	[
T3585	18514-18516	CD	denotes	19
T3586	18516-18517	,	denotes	,
T3584	18517-18519	CD	denotes	25
T3587	18519-18520	-RRB-	denotes	]
T3588	18520-18522	,	denotes	,
T3589	18522-18524	IN	denotes	as
T3590	18525-18528	VBP	denotes	are
T3591	18529-18534	NNS	denotes	cells
T3592	18535-18539	IN	denotes	from
T3593	18540-18541	DT	denotes	a
T3595	18542-18552	JJ	denotes	homozygous
T3596	18553-18559	JJ	denotes	viable
T3597	18560-18567	NN	denotes	XpdXPCS
T3599	18567-18568	HYPH	denotes	/
T3598	18568-18572	NN	denotes	XPCS
T3600	18573-18574	-LRB-	denotes	(
T3602	18574-18582	NN	denotes	XPDG602D
T3603	18582-18583	HYPH	denotes	/
T3601	18583-18588	NN	denotes	G602D
T3604	18588-18589	-RRB-	denotes	)
T3605	18590-18595	NN	denotes	mouse
T3594	18596-18601	NN	denotes	model
T3606	18602-18603	-LRB-	denotes	(
T3608	18603-18609	NN	denotes	Figure
T3607	18610-18612	NN	denotes	4A
T3609	18612-18614	,	denotes	,
T3610	18614-18620	VBN	denotes	dotted
T3611	18621-18625	NN	denotes	line
T3612	18625-18626	-RRB-	denotes	)
T3613	18627-18628	-LRB-	denotes	[
T3614	18628-18630	CD	denotes	23
T3615	18630-18631	-RRB-	denotes	]
T3616	18631-18632	.	denotes	.
T3617	18632-18793	sentence	denotes	Thus, the survival of XpdTTD/†XPCS (and XpdTTD/†XP) cells likely represents a level of UV resistance that neither mutant allele can impart on its own (Table 2).
T3618	18633-18637	RB	denotes	Thus
T3620	18637-18639	,	denotes	,
T3621	18639-18642	DT	denotes	the
T3622	18643-18651	NN	denotes	survival
T3623	18652-18654	IN	denotes	of
T3624	18655-18661	NN	denotes	XpdTTD
T3626	18661-18662	HYPH	denotes	/
T3625	18662-18667	NN	denotes	†XPCS
T3628	18668-18669	-LRB-	denotes	(
T3629	18669-18672	CC	denotes	and
T3630	18673-18679	NN	denotes	XpdTTD
T3632	18679-18680	HYPH	denotes	/
T3631	18680-18683	NN	denotes	†XP
T3633	18683-18684	-RRB-	denotes	)
T3627	18685-18690	NNS	denotes	cells
T3634	18691-18697	RB	denotes	likely
T3619	18698-18708	VBZ	denotes	represents
T3635	18709-18710	DT	denotes	a
T3636	18711-18716	NN	denotes	level
T3637	18717-18719	IN	denotes	of
T3638	18720-18722	NN	denotes	UV
T3639	18723-18733	NN	denotes	resistance
T3640	18734-18738	WDT	denotes	that
T3642	18739-18746	CC	denotes	neither
T3644	18747-18753	JJ	denotes	mutant
T3643	18754-18760	NN	denotes	allele
T3645	18761-18764	MD	denotes	can
T3641	18765-18771	VB	denotes	impart
T3646	18772-18774	IN	denotes	on
T3647	18775-18778	PRP$	denotes	its
T3648	18779-18782	NN	denotes	own
T3649	18783-18784	-LRB-	denotes	(
T3650	18784-18789	NN	denotes	Table
T3651	18790-18791	CD	denotes	2
T3652	18791-18792	-RRB-	denotes	)
T3653	18792-18793	.	denotes	.
T3654	18793-18951	sentence	denotes	Significant effects of compound heterozygosity on NER subpathways relative to XpdTTD/KO cells were observed in XpdTTD/†XP cells but only for UV-UDS activity.
T3655	18794-18805	JJ	denotes	Significant
T3656	18806-18813	NNS	denotes	effects
T3658	18814-18816	IN	denotes	of
T3659	18817-18825	NN	denotes	compound
T3660	18826-18840	NN	denotes	heterozygosity
T3661	18841-18843	IN	denotes	on
T3662	18844-18847	NN	denotes	NER
T3663	18848-18859	NNS	denotes	subpathways
T3664	18860-18868	JJ	denotes	relative
T3665	18869-18871	IN	denotes	to
T3666	18872-18878	NN	denotes	XpdTTD
T3668	18878-18879	HYPH	denotes	/
T3667	18879-18881	NN	denotes	KO
T3669	18882-18887	NNS	denotes	cells
T3670	18888-18892	VBD	denotes	were
T3657	18893-18901	VBN	denotes	observed
T3671	18902-18904	IN	denotes	in
T3672	18905-18911	NN	denotes	XpdTTD
T3674	18911-18912	HYPH	denotes	/
T3673	18912-18915	NN	denotes	†XP
T3675	18916-18921	NNS	denotes	cells
T3676	18922-18925	CC	denotes	but
T3677	18926-18930	RB	denotes	only
T3678	18931-18934	IN	denotes	for
T3679	18935-18937	NN	denotes	UV
T3681	18937-18938	HYPH	denotes	-
T3680	18938-18941	NN	denotes	UDS
T3682	18942-18950	NN	denotes	activity
T3683	18950-18951	.	denotes	.
T3684	18951-19200	sentence	denotes	Finally, none of the mutant TFIIH combinations (carrying alterations associated with TTD [XPDR722W], XPCS [XPDG602D], or XP [XPDR683W]) exhibited synergism in an in vitro NER reaction reconstituted with different mutant TFIIH complexes (Figure 4D).
T3685	18952-18959	RB	denotes	Finally
T3687	18959-18961	,	denotes	,
T3688	18961-18965	NN	denotes	none
T3689	18966-18968	IN	denotes	of
T3690	18969-18972	DT	denotes	the
T3692	18973-18979	JJ	denotes	mutant
T3693	18980-18985	NN	denotes	TFIIH
T3691	18986-18998	NNS	denotes	combinations
T3694	18999-19000	-LRB-	denotes	(
T3695	19000-19008	VBG	denotes	carrying
T3696	19009-19020	NNS	denotes	alterations
T3697	19021-19031	VBN	denotes	associated
T3698	19032-19036	IN	denotes	with
T3699	19037-19040	NN	denotes	TTD
T3700	19041-19042	-LRB-	denotes	[
T3701	19042-19050	NN	denotes	XPDR722W
T3702	19050-19051	-RRB-	denotes	]
T3703	19051-19053	,	denotes	,
T3704	19053-19057	NN	denotes	XPCS
T3705	19058-19059	-LRB-	denotes	[
T3706	19059-19067	NN	denotes	XPDG602D
T3707	19067-19068	-RRB-	denotes	]
T3708	19068-19070	,	denotes	,
T3709	19070-19072	CC	denotes	or
T3710	19073-19075	NN	denotes	XP
T3711	19076-19077	-LRB-	denotes	[
T3712	19077-19085	NN	denotes	XPDR683W
T3713	19085-19086	-RRB-	denotes	]
T3714	19086-19087	-RRB-	denotes	)
T3686	19088-19097	VBD	denotes	exhibited
T3715	19098-19107	NN	denotes	synergism
T3716	19108-19110	IN	denotes	in
T3717	19111-19113	DT	denotes	an
T3719	19114-19116	FW	denotes	in
T3720	19117-19122	FW	denotes	vitro
T3721	19123-19126	NN	denotes	NER
T3718	19127-19135	NN	denotes	reaction
T3722	19136-19149	VBN	denotes	reconstituted
T3723	19150-19154	IN	denotes	with
T3724	19155-19164	JJ	denotes	different
T3726	19165-19171	JJ	denotes	mutant
T3727	19172-19177	NN	denotes	TFIIH
T3725	19178-19187	NNS	denotes	complexes
T3728	19188-19189	-LRB-	denotes	(
T3730	19189-19195	NN	denotes	Figure
T3729	19196-19198	NN	denotes	4D
T3731	19198-19199	-RRB-	denotes	)
T3732	19199-19200	.	denotes	.
T3733	19200-19435	sentence	denotes	Taken together, these data are consistent with interallelic complementation of UV sensitivity in cells but underscore the lack of any correlation between UV-related repair characteristics and TTD progeroid phenotypes in animal models.
T3734	19201-19206	VBN	denotes	Taken
T3736	19207-19215	RB	denotes	together
T3737	19215-19217	,	denotes	,
T3738	19217-19222	DT	denotes	these
T3739	19223-19227	NNS	denotes	data
T3735	19228-19231	VBP	denotes	are
T3740	19232-19242	JJ	denotes	consistent
T3741	19243-19247	IN	denotes	with
T3742	19248-19260	JJ	denotes	interallelic
T3743	19261-19276	NN	denotes	complementation
T3744	19277-19279	IN	denotes	of
T3745	19280-19282	NN	denotes	UV
T3746	19283-19294	NN	denotes	sensitivity
T3747	19295-19297	IN	denotes	in
T3748	19298-19303	NNS	denotes	cells
T3749	19304-19307	CC	denotes	but
T3750	19308-19318	VBP	denotes	underscore
T3751	19319-19322	DT	denotes	the
T3752	19323-19327	NN	denotes	lack
T3753	19328-19330	IN	denotes	of
T3754	19331-19334	DT	denotes	any
T3755	19335-19346	NN	denotes	correlation
T3756	19347-19354	IN	denotes	between
T3757	19355-19357	NN	denotes	UV
T3759	19357-19358	HYPH	denotes	-
T3758	19358-19365	VBN	denotes	related
T3761	19366-19372	NN	denotes	repair
T3760	19373-19388	NNS	denotes	characteristics
T3762	19389-19392	CC	denotes	and
T3763	19393-19396	NN	denotes	TTD
T3765	19397-19406	NN	denotes	progeroid
T3764	19407-19417	NNS	denotes	phenotypes
T3766	19418-19420	IN	denotes	in
T3767	19421-19427	NN	denotes	animal
T3768	19428-19434	NNS	denotes	models
T3769	19434-19435	.	denotes	.
T3770	19435-19436	sentence	denotes
T8564	19446-19451	NN	denotes	TFIIH
T8565	19452-19461	NNS	denotes	Functions
T8566	19462-19465	CC	denotes	and
T8567	19466-19476	NNS	denotes	Mechanisms
T8568	19477-19479	IN	denotes	of
T8569	19480-19483	NN	denotes	XPD
T8571	19483-19484	HYPH	denotes	-
T8570	19484-19494	VBN	denotes	Associated
T8573	19495-19502	NN	denotes	Disease
T8572	19503-19513	NN	denotes	Pleiotropy
T8574	19513-19557	sentence	denotes	(A) Cellular survival after UV irradiation.
T8575	19514-19515	-LRB-	denotes	(
T8576	19515-19516	LS	denotes	A
T8578	19516-19517	-RRB-	denotes	)
T8579	19518-19526	JJ	denotes	Cellular
T8577	19527-19535	NN	denotes	survival
T8580	19536-19541	IN	denotes	after
T8581	19542-19544	NN	denotes	UV
T8582	19545-19556	NN	denotes	irradiation
T8583	19556-19557	.	denotes	.
T8584	19557-19683	sentence	denotes	Rescue of hemizygous XpdTTD/KO survival by Xpd†XPCS and Xpd†XP alleles is illustrated by arrows marked A and B, respectively.
T8585	19558-19564	NN	denotes	Rescue
T8587	19565-19567	IN	denotes	of
T8588	19568-19578	JJ	denotes	hemizygous
T8590	19579-19585	NN	denotes	XpdTTD
T8592	19585-19586	HYPH	denotes	/
T8591	19586-19588	NN	denotes	KO
T8589	19589-19597	NN	denotes	survival
T8593	19598-19600	IN	denotes	by
T8594	19601-19609	NN	denotes	Xpd†XPCS
T8596	19610-19613	CC	denotes	and
T8597	19614-19620	NN	denotes	Xpd†XP
T8595	19621-19628	NNS	denotes	alleles
T8598	19629-19631	VBZ	denotes	is
T8586	19632-19643	VBN	denotes	illustrated
T8599	19644-19646	IN	denotes	by
T8600	19647-19653	NNS	denotes	arrows
T8601	19654-19660	VBN	denotes	marked
T8602	19661-19662	NN	denotes	A
T8603	19663-19666	CC	denotes	and
T8604	19667-19668	NN	denotes	B
T8605	19668-19670	,	denotes	,
T8606	19670-19682	RB	denotes	respectively
T8607	19682-19683	.	denotes	.
T8608	19683-19821	sentence	denotes	UV survival of homozygous XpdXPCS/XPCS cells (asterisk) from the normally expressed viable allele (XpdXPCS) is depicted by a dotted line.
T8609	19684-19686	NN	denotes	UV
T8610	19687-19695	NN	denotes	survival
T8612	19696-19698	IN	denotes	of
T8613	19699-19709	JJ	denotes	homozygous
T8615	19710-19717	NN	denotes	XpdXPCS
T8617	19717-19718	HYPH	denotes	/
T8616	19718-19722	NN	denotes	XPCS
T8614	19723-19728	NNS	denotes	cells
T8618	19729-19730	-LRB-	denotes	(
T8619	19730-19738	NN	denotes	asterisk
T8620	19738-19739	-RRB-	denotes	)
T8621	19740-19744	IN	denotes	from
T8622	19745-19748	DT	denotes	the
T8624	19749-19757	RB	denotes	normally
T8625	19758-19767	VBN	denotes	expressed
T8626	19768-19774	JJ	denotes	viable
T8623	19775-19781	NN	denotes	allele
T8627	19782-19783	-LRB-	denotes	(
T8628	19783-19790	NN	denotes	XpdXPCS
T8629	19790-19791	-RRB-	denotes	)
T8630	19792-19794	VBZ	denotes	is
T8611	19795-19803	VBN	denotes	depicted
T8631	19804-19806	IN	denotes	by
T8632	19807-19808	DT	denotes	a
T8634	19809-19815	VBN	denotes	dotted
T8633	19816-19820	NN	denotes	line
T8635	19820-19821	.	denotes	.
T8636	19821-19953	sentence	denotes	Survival curves represent an average of four independent experiments; 1–2 cell lines per genotype were included in each experiment.
T8637	19822-19830	NN	denotes	Survival
T8638	19831-19837	NNS	denotes	curves
T8639	19838-19847	VBP	denotes	represent
T8641	19848-19850	DT	denotes	an
T8642	19851-19858	NN	denotes	average
T8643	19859-19861	IN	denotes	of
T8644	19862-19866	CD	denotes	four
T8646	19867-19878	JJ	denotes	independent
T8645	19879-19890	NNS	denotes	experiments
T8647	19890-19891	:	denotes	;
T8648	19892-19893	CD	denotes	1
T8650	19893-19894	SYM	denotes	–
T8649	19894-19895	CD	denotes	2
T8652	19896-19900	NN	denotes	cell
T8651	19901-19906	NNS	denotes	lines
T8653	19907-19910	IN	denotes	per
T8654	19911-19919	NN	denotes	genotype
T8655	19920-19924	VBD	denotes	were
T8640	19925-19933	VBN	denotes	included
T8656	19934-19936	IN	denotes	in
T8657	19937-19941	DT	denotes	each
T8658	19942-19952	NN	denotes	experiment
T8659	19952-19953	.	denotes	.
T8660	19953-19998	sentence	denotes	Error bars indicate SEM between experiments.
T8661	19954-19959	NN	denotes	Error
T8662	19960-19964	NNS	denotes	bars
T8663	19965-19973	VBP	denotes	indicate
T8664	19974-19977	NN	denotes	SEM
T8665	19978-19985	IN	denotes	between
T8666	19986-19997	NNS	denotes	experiments
T8667	19997-19998	.	denotes	.
T8668	19998-20045	sentence	denotes	(B) UV-UDS, a measure of global genome repair.
T8669	19999-20000	-LRB-	denotes	(
T8670	20000-20001	LS	denotes	B
T8672	20001-20002	-RRB-	denotes	)
T8673	20003-20005	NN	denotes	UV
T8674	20005-20006	HYPH	denotes	-
T8671	20006-20009	NN	denotes	UDS
T8675	20009-20011	,	denotes	,
T8676	20011-20012	DT	denotes	a
T8677	20013-20020	NN	denotes	measure
T8678	20021-20023	IN	denotes	of
T8679	20024-20030	JJ	denotes	global
T8681	20031-20037	NN	denotes	genome
T8680	20038-20044	NN	denotes	repair
T8682	20044-20045	.	denotes	.
T8683	20045-20214	sentence	denotes	Number of experiments: n = 15 (XpdTTD/TTD), n = 6 (XpdTTD/KO), n = 4 (XpdTTD/†XPCS ), n = 2 (XpdTTD/†XP ); 1–2 cell lines per genotype were included in each experiment.
T8684	20046-20052	NN	denotes	Number
T8686	20053-20055	IN	denotes	of
T8687	20056-20067	NNS	denotes	experiments
T8688	20067-20069	:	denotes	:
T8689	20069-20070	NN	denotes	n
T8691	20071-20072	SYM	denotes	=
T8690	20073-20075	CD	denotes	15
T8692	20076-20077	-LRB-	denotes	(
T8693	20077-20083	NN	denotes	XpdTTD
T8694	20083-20084	SYM	denotes	/
T8695	20084-20087	NN	denotes	TTD
T8696	20087-20088	-RRB-	denotes	)
T8697	20088-20090	,	denotes	,
T8698	20090-20091	NN	denotes	n
T8700	20092-20093	SYM	denotes	=
T8699	20094-20095	CD	denotes	6
T8701	20096-20097	-LRB-	denotes	(
T8703	20097-20103	NN	denotes	XpdTTD
T8704	20103-20104	HYPH	denotes	/
T8702	20104-20106	NN	denotes	KO
T8705	20106-20107	-RRB-	denotes	)
T8706	20107-20109	,	denotes	,
T8707	20109-20110	NN	denotes	n
T8709	20111-20112	SYM	denotes	=
T8708	20113-20114	CD	denotes	4
T8710	20115-20116	-LRB-	denotes	(
T8712	20116-20122	NN	denotes	XpdTTD
T8713	20122-20123	HYPH	denotes	/
T8711	20123-20128	NN	denotes	†XPCS
T8714	20129-20130	-RRB-	denotes	)
T8715	20130-20132	,	denotes	,
T8716	20132-20133	NN	denotes	n
T8718	20134-20135	SYM	denotes	=
T8717	20136-20137	CD	denotes	2
T8719	20138-20139	-LRB-	denotes	(
T8721	20139-20145	NN	denotes	XpdTTD
T8722	20145-20146	HYPH	denotes	/
T8720	20146-20149	NN	denotes	†XP
T8723	20150-20151	-RRB-	denotes	)
T8724	20151-20152	:	denotes	;
T8725	20153-20154	CD	denotes	1
T8727	20154-20155	SYM	denotes	–
T8726	20155-20156	CD	denotes	2
T8729	20157-20161	NN	denotes	cell
T8728	20162-20167	NNS	denotes	lines
T8730	20168-20171	IN	denotes	per
T8731	20172-20180	NN	denotes	genotype
T8732	20181-20185	VBD	denotes	were
T8685	20186-20194	VBN	denotes	included
T8733	20195-20197	IN	denotes	in
T8734	20198-20202	DT	denotes	each
T8735	20203-20213	NN	denotes	experiment
T8736	20213-20214	.	denotes	.
T8737	20214-20334	sentence	denotes	The asterisk indicates significant difference with XpdTTD/TTD; crosses indicate significant differences with XpdTTD/KO.
T8738	20215-20218	DT	denotes	The
T8739	20219-20227	NN	denotes	asterisk
T8740	20228-20237	VBZ	denotes	indicates
T8742	20238-20249	JJ	denotes	significant
T8743	20250-20260	NN	denotes	difference
T8744	20261-20265	IN	denotes	with
T8745	20266-20272	NN	denotes	XpdTTD
T8747	20272-20273	HYPH	denotes	/
T8746	20273-20276	NN	denotes	TTD
T8748	20276-20277	:	denotes	;
T8749	20278-20285	NNS	denotes	crosses
T8741	20286-20294	VBP	denotes	indicate
T8750	20295-20306	JJ	denotes	significant
T8751	20307-20318	NNS	denotes	differences
T8752	20319-20323	IN	denotes	with
T8753	20324-20330	NN	denotes	XpdTTD
T8755	20330-20331	HYPH	denotes	/
T8754	20331-20333	NN	denotes	KO
T8756	20333-20334	.	denotes	.
T8757	20334-20411	sentence	denotes	(C) UV-RRS, a measure of transcription-coupled repair of UV-induced lesions.
T8758	20335-20336	-LRB-	denotes	(
T8759	20336-20337	LS	denotes	C
T8761	20337-20338	-RRB-	denotes	)
T8762	20339-20341	NN	denotes	UV
T8763	20341-20342	HYPH	denotes	-
T8760	20342-20345	NN	denotes	RRS
T8764	20345-20347	,	denotes	,
T8765	20347-20348	DT	denotes	a
T8766	20349-20356	NN	denotes	measure
T8767	20357-20359	IN	denotes	of
T8768	20360-20373	NN	denotes	transcription
T8770	20373-20374	HYPH	denotes	-
T8769	20374-20381	VBN	denotes	coupled
T8771	20382-20388	NN	denotes	repair
T8772	20389-20391	IN	denotes	of
T8773	20392-20394	NN	denotes	UV
T8775	20394-20395	HYPH	denotes	-
T8774	20395-20402	VBN	denotes	induced
T8776	20403-20410	NNS	denotes	lesions
T8777	20410-20411	.	denotes	.
T8778	20411-20579	sentence	denotes	Number of experiments: n = 7 (XpdTTD/TTD), n = 2 (XpdTTD/KO), n = 4 (XpdTTD/†XPCS ), n = 2 (XpdTTD/†XP ); 1–2 cell lines per genotype were included in each experiment.
T8779	20412-20418	NN	denotes	Number
T8781	20419-20421	IN	denotes	of
T8782	20422-20433	NNS	denotes	experiments
T8783	20433-20435	:	denotes	:
T8784	20435-20436	NN	denotes	n
T8786	20437-20438	SYM	denotes	=
T8785	20439-20440	CD	denotes	7
T8787	20441-20442	-LRB-	denotes	(
T8789	20442-20448	NN	denotes	XpdTTD
T8790	20448-20449	HYPH	denotes	/
T8788	20449-20452	NN	denotes	TTD
T8791	20452-20453	-RRB-	denotes	)
T8792	20453-20455	,	denotes	,
T8793	20455-20456	NN	denotes	n
T8795	20457-20458	SYM	denotes	=
T8794	20459-20460	CD	denotes	2
T8796	20461-20462	-LRB-	denotes	(
T8798	20462-20468	NN	denotes	XpdTTD
T8799	20468-20469	HYPH	denotes	/
T8797	20469-20471	NN	denotes	KO
T8800	20471-20472	-RRB-	denotes	)
T8801	20472-20474	,	denotes	,
T8802	20474-20475	NN	denotes	n
T8804	20476-20477	SYM	denotes	=
T8803	20478-20479	CD	denotes	4
T8805	20480-20481	-LRB-	denotes	(
T8807	20481-20487	NN	denotes	XpdTTD
T8808	20487-20488	HYPH	denotes	/
T8806	20488-20493	NN	denotes	†XPCS
T8809	20494-20495	-RRB-	denotes	)
T8810	20495-20497	,	denotes	,
T8811	20497-20498	NN	denotes	n
T8813	20499-20500	SYM	denotes	=
T8812	20501-20502	CD	denotes	2
T8814	20503-20504	-LRB-	denotes	(
T8816	20504-20510	NN	denotes	XpdTTD
T8817	20510-20511	HYPH	denotes	/
T8815	20511-20514	NN	denotes	†XP
T8818	20515-20516	-RRB-	denotes	)
T8819	20516-20517	:	denotes	;
T8820	20518-20519	CD	denotes	1
T8822	20519-20520	SYM	denotes	–
T8821	20520-20521	CD	denotes	2
T8824	20522-20526	NN	denotes	cell
T8823	20527-20532	NNS	denotes	lines
T8825	20533-20536	IN	denotes	per
T8826	20537-20545	NN	denotes	genotype
T8827	20546-20550	VBD	denotes	were
T8780	20551-20559	VBN	denotes	included
T8828	20560-20562	IN	denotes	in
T8829	20563-20567	DT	denotes	each
T8830	20568-20578	NN	denotes	experiment
T8831	20578-20579	.	denotes	.
T8832	20579-20686	sentence	denotes	(D) Incision/excision activity of combinations of altered TFIIH complexes in a reconstituted NER reaction.
T8833	20580-20581	-LRB-	denotes	(
T8834	20581-20582	LS	denotes	D
T8836	20582-20583	-RRB-	denotes	)
T8837	20584-20592	NN	denotes	Incision
T8839	20592-20593	HYPH	denotes	/
T8838	20593-20601	NN	denotes	excision
T8835	20602-20610	NN	denotes	activity
T8840	20611-20613	IN	denotes	of
T8841	20614-20626	NNS	denotes	combinations
T8842	20627-20629	IN	denotes	of
T8843	20630-20637	VBN	denotes	altered
T8845	20638-20643	NN	denotes	TFIIH
T8844	20644-20653	NNS	denotes	complexes
T8846	20654-20656	IN	denotes	in
T8847	20657-20658	DT	denotes	a
T8849	20659-20672	VBN	denotes	reconstituted
T8850	20673-20676	NN	denotes	NER
T8848	20677-20685	NN	denotes	reaction
T8851	20685-20686	.	denotes	.
T8852	20686-20940	sentence	denotes	Equal amounts of single or mixed populations of recombinant TFIIHs (containing XPD, XPB, p62, p52, His-p44, Flag-p34, cdk7, cyclin H, Mat1, and p8) were mixed with recombinant XPG, XPF/ERCC1, XPC/hHR23B, RPA, and a radiolabelled synthetic NER substrate.
T8853	20687-20692	JJ	denotes	Equal
T8854	20693-20700	NNS	denotes	amounts
T8856	20701-20703	IN	denotes	of
T8857	20704-20710	JJ	denotes	single
T8859	20711-20713	CC	denotes	or
T8860	20714-20719	JJ	denotes	mixed
T8858	20720-20731	NNS	denotes	populations
T8861	20732-20734	IN	denotes	of
T8862	20735-20746	JJ	denotes	recombinant
T8863	20747-20753	NNS	denotes	TFIIHs
T8864	20754-20755	-LRB-	denotes	(
T8865	20755-20765	VBG	denotes	containing
T8866	20766-20769	NN	denotes	XPD
T8867	20769-20771	,	denotes	,
T8868	20771-20774	NN	denotes	XPB
T8869	20774-20776	,	denotes	,
T8870	20776-20779	NN	denotes	p62
T8871	20779-20781	,	denotes	,
T8872	20781-20784	NN	denotes	p52
T8873	20784-20786	,	denotes	,
T8874	20786-20789	NN	denotes	His
T8876	20789-20790	HYPH	denotes	-
T8875	20790-20793	NN	denotes	p44
T8877	20793-20795	,	denotes	,
T8878	20795-20799	NN	denotes	Flag
T8880	20799-20800	HYPH	denotes	-
T8879	20800-20803	NN	denotes	p34
T8881	20803-20805	,	denotes	,
T8882	20805-20809	NN	denotes	cdk7
T8883	20809-20811	,	denotes	,
T8884	20811-20817	NN	denotes	cyclin
T8885	20818-20819	NN	denotes	H
T8886	20819-20821	,	denotes	,
T8887	20821-20825	NN	denotes	Mat1
T8888	20825-20827	,	denotes	,
T8889	20827-20830	CC	denotes	and
T8890	20831-20833	NN	denotes	p8
T8891	20833-20834	-RRB-	denotes	)
T8892	20835-20839	VBD	denotes	were
T8855	20840-20845	VBN	denotes	mixed
T8893	20846-20850	IN	denotes	with
T8894	20851-20862	JJ	denotes	recombinant
T8895	20863-20866	NN	denotes	XPG
T8896	20866-20868	,	denotes	,
T8897	20868-20871	NN	denotes	XPF
T8899	20871-20872	HYPH	denotes	/
T8898	20872-20877	NN	denotes	ERCC1
T8900	20877-20879	,	denotes	,
T8901	20879-20882	NN	denotes	XPC
T8903	20882-20883	HYPH	denotes	/
T8902	20883-20889	NN	denotes	hHR23B
T8904	20889-20891	,	denotes	,
T8905	20891-20894	NN	denotes	RPA
T8906	20894-20896	,	denotes	,
T8907	20896-20899	CC	denotes	and
T8908	20900-20901	DT	denotes	a
T8910	20902-20915	VBN	denotes	radiolabelled
T8911	20916-20925	JJ	denotes	synthetic
T8912	20926-20929	NN	denotes	NER
T8909	20930-20939	NN	denotes	substrate
T8913	20939-20940	.	denotes	.
T8914	20940-21083	sentence	denotes	The excision products (26–34 nucleotides in length) were visualised at nucleotide resolution on a denaturing polyacrylamide gel as indicated .
T8915	20941-20944	DT	denotes	The
T8917	20945-20953	NN	denotes	excision
T8916	20954-20962	NNS	denotes	products
T8919	20963-20964	-LRB-	denotes	(
T8921	20964-20966	CD	denotes	26
T8923	20966-20967	SYM	denotes	–
T8922	20967-20969	CD	denotes	34
T8920	20970-20981	NNS	denotes	nucleotides
T8924	20982-20984	IN	denotes	in
T8925	20985-20991	NN	denotes	length
T8926	20991-20992	-RRB-	denotes	)
T8927	20993-20997	VBD	denotes	were
T8918	20998-21008	VBN	denotes	visualised
T8928	21009-21011	IN	denotes	at
T8929	21012-21022	NN	denotes	nucleotide
T8930	21023-21033	NN	denotes	resolution
T8931	21034-21036	IN	denotes	on
T8932	21037-21038	DT	denotes	a
T8934	21039-21049	VBG	denotes	denaturing
T8935	21050-21064	NN	denotes	polyacrylamide
T8933	21065-21068	NN	denotes	gel
T8936	21069-21071	IN	denotes	as
T8937	21072-21081	VBN	denotes	indicated
T8938	21082-21083	.	denotes	.
T8939	21083-21234	sentence	denotes	Note the weak activity corresponding to each single and combined TFIIH complex (lanes 3–8) relative to the wt (lane 1) and negative controls (lane 2).
T8940	21084-21088	VB	denotes	Note
T8941	21089-21092	DT	denotes	the
T8943	21093-21097	JJ	denotes	weak
T8942	21098-21106	NN	denotes	activity
T8944	21107-21120	VBG	denotes	corresponding
T8945	21121-21123	IN	denotes	to
T8946	21124-21128	DT	denotes	each
T8948	21129-21135	JJ	denotes	single
T8949	21136-21139	CC	denotes	and
T8950	21140-21148	VBN	denotes	combined
T8951	21149-21154	NN	denotes	TFIIH
T8947	21155-21162	NN	denotes	complex
T8952	21163-21164	-LRB-	denotes	(
T8954	21164-21169	NNS	denotes	lanes
T8953	21170-21171	CD	denotes	3
T8955	21171-21172	SYM	denotes	–
T8956	21172-21173	CD	denotes	8
T8957	21173-21174	-RRB-	denotes	)
T8958	21175-21183	JJ	denotes	relative
T8959	21184-21186	IN	denotes	to
T8960	21187-21190	DT	denotes	the
T8961	21191-21193	NN	denotes	wt
T8962	21194-21195	-LRB-	denotes	(
T8963	21195-21199	NN	denotes	lane
T8964	21200-21201	CD	denotes	1
T8965	21201-21202	-RRB-	denotes	)
T8966	21203-21206	CC	denotes	and
T8967	21207-21215	JJ	denotes	negative
T8968	21216-21224	NNS	denotes	controls
T8969	21225-21226	-LRB-	denotes	(
T8970	21226-21230	NN	denotes	lane
T8971	21231-21232	CD	denotes	2
T8972	21232-21233	-RRB-	denotes	)
T8973	21233-21234	.	denotes	.
T8974	21234-21447	sentence	denotes	(E) Xpd dose-dependent reduction of TFIIH in homozygous XpdTTD/TTD, hemizygous XpdTTD/KO, and compound heterozygous XpdTTD/†XPCS and XpdTTD/†XP cells by comparative immunofluorescence of the p62 subunit of TFIIH.
T8975	21235-21236	-LRB-	denotes	(
T8976	21236-21237	LS	denotes	E
T8978	21237-21238	-RRB-	denotes	)
T8979	21239-21242	NN	denotes	Xpd
T8980	21243-21247	NN	denotes	dose
T8982	21247-21248	HYPH	denotes	-
T8981	21248-21257	JJ	denotes	dependent
T8977	21258-21267	NN	denotes	reduction
T8983	21268-21270	IN	denotes	of
T8984	21271-21276	NN	denotes	TFIIH
T8985	21277-21279	IN	denotes	in
T8986	21280-21290	JJ	denotes	homozygous
T8988	21291-21297	NN	denotes	XpdTTD
T8989	21297-21298	HYPH	denotes	/
T8987	21298-21301	NN	denotes	TTD
T8991	21301-21303	,	denotes	,
T8992	21303-21313	JJ	denotes	hemizygous
T8994	21314-21320	NN	denotes	XpdTTD
T8995	21320-21321	HYPH	denotes	/
T8993	21321-21323	NN	denotes	KO
T8996	21323-21325	,	denotes	,
T8997	21325-21328	CC	denotes	and
T8998	21329-21337	NN	denotes	compound
T9000	21338-21350	JJ	denotes	heterozygous
T9001	21351-21357	NN	denotes	XpdTTD
T9002	21357-21358	HYPH	denotes	/
T8999	21358-21363	NN	denotes	†XPCS
T9003	21364-21367	CC	denotes	and
T9004	21368-21374	NN	denotes	XpdTTD
T9006	21374-21375	HYPH	denotes	/
T9005	21375-21378	NN	denotes	†XP
T8990	21379-21384	NNS	denotes	cells
T9007	21385-21387	IN	denotes	by
T9008	21388-21399	JJ	denotes	comparative
T9009	21400-21418	NN	denotes	immunofluorescence
T9010	21419-21421	IN	denotes	of
T9011	21422-21425	DT	denotes	the
T9013	21426-21429	NN	denotes	p62
T9012	21430-21437	NN	denotes	subunit
T9014	21438-21440	IN	denotes	of
T9015	21441-21446	NN	denotes	TFIIH
T9016	21446-21447	.	denotes	.
T9017	21447-21865	sentence	denotes	Roman numerals represent different microscopic slides and Arabic numerals different cell lines labelled as follows: (I) wt cells (1) labelled with 2-μm beads, XpdTTD/TTD cells (2) with 0.79-μm beads, and XpdTTD/KO cells (3) with no beads; (II) wt cells (1) labelled with 0.79-μm beads and XpdTTD/†XPCS cells (4) with no beads; and (III) wt cells (1) labelled with 0.79-μm beads and XpdTTD/†XP cells (5) with no beads.
T9018	21448-21453	JJ	denotes	Roman
T9019	21454-21462	NNS	denotes	numerals
T9020	21463-21472	VBP	denotes	represent
T9021	21473-21482	JJ	denotes	different
T9023	21483-21494	JJ	denotes	microscopic
T9022	21495-21501	NNS	denotes	slides
T9024	21502-21505	CC	denotes	and
T9025	21506-21512	JJ	denotes	Arabic
T9026	21513-21521	NNS	denotes	numerals
T9028	21522-21531	JJ	denotes	different
T9029	21532-21536	NN	denotes	cell
T9027	21537-21542	NNS	denotes	lines
T9030	21543-21551	VBN	denotes	labelled
T9031	21552-21554	IN	denotes	as
T9032	21555-21562	VBZ	denotes	follows
T9033	21562-21564	:	denotes	:
T9034	21564-21565	-LRB-	denotes	(
T9035	21565-21566	LS	denotes	I
T9037	21566-21567	-RRB-	denotes	)
T9038	21568-21570	NN	denotes	wt
T9036	21571-21576	NNS	denotes	cells
T9039	21577-21578	-LRB-	denotes	(
T9040	21578-21579	CD	denotes	1
T9041	21579-21580	-RRB-	denotes	)
T9042	21581-21589	VBN	denotes	labelled
T9043	21590-21594	IN	denotes	with
T9044	21595-21596	CD	denotes	2
T9046	21596-21597	HYPH	denotes	-
T9045	21597-21599	NN	denotes	μm
T9047	21600-21605	NNS	denotes	beads
T9048	21605-21607	,	denotes	,
T9049	21607-21613	NN	denotes	XpdTTD
T9051	21613-21614	HYPH	denotes	/
T9050	21614-21617	NN	denotes	TTD
T9052	21618-21623	NNS	denotes	cells
T9053	21624-21625	-LRB-	denotes	(
T9054	21625-21626	CD	denotes	2
T9055	21626-21627	-RRB-	denotes	)
T9056	21628-21632	IN	denotes	with
T9057	21633-21637	CD	denotes	0.79
T9059	21637-21638	HYPH	denotes	-
T9058	21638-21640	NN	denotes	μm
T9060	21641-21646	NNS	denotes	beads
T9061	21646-21648	,	denotes	,
T9062	21648-21651	CC	denotes	and
T9063	21652-21658	NN	denotes	XpdTTD
T9065	21658-21659	HYPH	denotes	/
T9064	21659-21661	NN	denotes	KO
T9066	21662-21667	NNS	denotes	cells
T9067	21668-21669	-LRB-	denotes	(
T9068	21669-21670	CD	denotes	3
T9069	21670-21671	-RRB-	denotes	)
T9070	21672-21676	IN	denotes	with
T9071	21677-21679	DT	denotes	no
T9072	21680-21685	NNS	denotes	beads
T9073	21685-21686	:	denotes	;
T9074	21687-21688	-LRB-	denotes	(
T9075	21688-21690	LS	denotes	II
T9077	21690-21691	-RRB-	denotes	)
T9078	21692-21694	NN	denotes	wt
T9076	21695-21700	NNS	denotes	cells
T9079	21701-21702	-LRB-	denotes	(
T9080	21702-21703	CD	denotes	1
T9081	21703-21704	-RRB-	denotes	)
T9082	21705-21713	VBN	denotes	labelled
T9083	21714-21718	IN	denotes	with
T9084	21719-21723	CD	denotes	0.79
T9086	21723-21724	HYPH	denotes	-
T9085	21724-21726	NN	denotes	μm
T9087	21727-21732	NNS	denotes	beads
T9088	21733-21736	CC	denotes	and
T9089	21737-21743	NN	denotes	XpdTTD
T9091	21743-21744	HYPH	denotes	/
T9090	21744-21749	NN	denotes	†XPCS
T9092	21750-21755	NNS	denotes	cells
T9093	21756-21757	-LRB-	denotes	(
T9094	21757-21758	CD	denotes	4
T9095	21758-21759	-RRB-	denotes	)
T9096	21760-21764	IN	denotes	with
T9097	21765-21767	DT	denotes	no
T9098	21768-21773	NNS	denotes	beads
T9099	21773-21774	:	denotes	;
T9100	21775-21778	CC	denotes	and
T9101	21779-21780	-LRB-	denotes	(
T9102	21780-21783	LS	denotes	III
T9104	21783-21784	-RRB-	denotes	)
T9105	21785-21787	NN	denotes	wt
T9103	21788-21793	NNS	denotes	cells
T9106	21794-21795	-LRB-	denotes	(
T9107	21795-21796	CD	denotes	1
T9108	21796-21797	-RRB-	denotes	)
T9109	21798-21806	VBN	denotes	labelled
T9110	21807-21811	IN	denotes	with
T9111	21812-21816	CD	denotes	0.79
T9113	21816-21817	HYPH	denotes	-
T9112	21817-21819	NN	denotes	μm
T9114	21820-21825	NNS	denotes	beads
T9115	21826-21829	CC	denotes	and
T9116	21830-21836	NN	denotes	XpdTTD
T9118	21836-21837	HYPH	denotes	/
T9117	21837-21840	NN	denotes	†XP
T9119	21841-21846	NNS	denotes	cells
T9120	21847-21848	-LRB-	denotes	(
T9121	21848-21849	CD	denotes	5
T9122	21849-21850	-RRB-	denotes	)
T9123	21851-21855	IN	denotes	with
T9124	21856-21858	DT	denotes	no
T9125	21859-21864	NNS	denotes	beads
T9126	21864-21865	.	denotes	.
T9127	21865-21984	sentence	denotes	(F) Quantification of immunofluorescent signal from at least 50 nuclei per cell line and 2–6 experiments per genotype.
T9128	21866-21867	-LRB-	denotes	(
T9129	21867-21868	LS	denotes	F
T9131	21868-21869	-RRB-	denotes	)
T9130	21870-21884	NN	denotes	Quantification
T9132	21885-21887	IN	denotes	of
T9133	21888-21905	JJ	denotes	immunofluorescent
T9134	21906-21912	NN	denotes	signal
T9135	21913-21917	IN	denotes	from
T9136	21918-21920	RB	denotes	at
T9138	21921-21926	RBS	denotes	least
T9137	21927-21929	CD	denotes	50
T9139	21930-21936	NNS	denotes	nuclei
T9140	21937-21940	IN	denotes	per
T9141	21941-21945	NN	denotes	cell
T9142	21946-21950	NN	denotes	line
T9143	21951-21954	CC	denotes	and
T9144	21955-21956	CD	denotes	2
T9146	21956-21957	SYM	denotes	–
T9145	21957-21958	CD	denotes	6
T9147	21959-21970	NNS	denotes	experiments
T9148	21971-21974	IN	denotes	per
T9149	21975-21983	NN	denotes	genotype
T9150	21983-21984	.	denotes	.
T9151	21984-22095	sentence	denotes	Bars representing cells analysed on the same microscopic slide are depicted side by side, with wt set at 100%.
T9152	21985-21989	NNS	denotes	Bars
T9154	21990-22002	VBG	denotes	representing
T9155	22003-22008	NNS	denotes	cells
T9156	22009-22017	VBN	denotes	analysed
T9157	22018-22020	IN	denotes	on
T9158	22021-22024	DT	denotes	the
T9160	22025-22029	JJ	denotes	same
T9161	22030-22041	JJ	denotes	microscopic
T9159	22042-22047	NN	denotes	slide
T9162	22048-22051	VBP	denotes	are
T9153	22052-22060	VBN	denotes	depicted
T9163	22061-22065	NN	denotes	side
T9164	22066-22068	IN	denotes	by
T9165	22069-22073	NN	denotes	side
T9166	22073-22075	,	denotes	,
T9167	22075-22079	IN	denotes	with
T9168	22080-22082	NN	denotes	wt
T9169	22083-22086	VBN	denotes	set
T9170	22087-22089	IN	denotes	at
T9171	22090-22093	CD	denotes	100
T9172	22093-22094	NN	denotes	%
T9173	22094-22095	.	denotes	.
T9174	22095-22250	sentence	denotes	The p-value indicates minimum significant difference between wt and the indicated cell lines analysed on the same microscopic slide within one experiment.
T9175	22096-22099	DT	denotes	The
T9177	22100-22101	NN	denotes	p
T9178	22101-22102	HYPH	denotes	-
T9176	22102-22107	NN	denotes	value
T9179	22108-22117	VBZ	denotes	indicates
T9180	22118-22125	JJ	denotes	minimum
T9182	22126-22137	JJ	denotes	significant
T9181	22138-22148	NN	denotes	difference
T9183	22149-22156	IN	denotes	between
T9184	22157-22159	NN	denotes	wt
T9185	22160-22163	CC	denotes	and
T9186	22164-22167	DT	denotes	the
T9188	22168-22177	VBN	denotes	indicated
T9189	22178-22182	NN	denotes	cell
T9187	22183-22188	NNS	denotes	lines
T9190	22189-22197	VBN	denotes	analysed
T9191	22198-22200	IN	denotes	on
T9192	22201-22204	DT	denotes	the
T9194	22205-22209	JJ	denotes	same
T9195	22210-22221	JJ	denotes	microscopic
T9193	22222-22227	NN	denotes	slide
T9196	22228-22234	IN	denotes	within
T9197	22235-22238	CD	denotes	one
T9198	22239-22249	NN	denotes	experiment
T9199	22249-22250	.	denotes	.
T3772	22251-22253	NN	denotes	Ne
T3771	22251-22260	sentence	denotes	Next we a
T3773	22253-22255	NNS	denotes	xt
T3774	22255-22256	:	denotes
T3775	22256-22258	VBD	denotes	we
T3776	22259-22260	DT	denotes	a
T3778	22260-22262	NN	denotes	sk
T3777	22260-22270	sentence	denotes	sked wheth
T3779	22262-22263	VBZ	denotes	e
T3781	22263-22264	NN	denotes	d
T3782	22265-22267	IN	denotes	wh
T3783	22267-22268	NNS	denotes	e
T3780	22268-22269	VBP	denotes	t
T3784	22269-22270	IN	denotes	h
T3786	22270-22272	NN	denotes	er
T3785	22270-22274	sentence	denotes	er t
T3787	22273-22274	NN	denotes	t
T3789	22274-22275	DT	denotes	h
T3788	22274-22276	sentence	denotes	he
T3790	22275-22276	NN	denotes	e
T3791	22276-22277	sentence	denotes
T3793	22277-22278	NN	denotes	X
T3792	22277-22280	sentence	denotes	Xpd
T3794	22278-22279	NN	denotes	p
T3795	22279-22280	NN	denotes	d
T3797	22280-22285	NN	denotes	†XPCS
T3796	22280-22299	sentence	denotes	†XPCS and Xpd†XP al
T3798	22286-22289	CC	denotes	and
T3799	22290-22293	NN	denotes	Xpd
T3800	22293-22296	NN	denotes	†XP
T3801	22297-22298	JJ	denotes	a
T3802	22298-22299	NN	denotes	l
T3804	22299-22300	NNS	denotes	l
T3803	22299-22317	sentence	denotes	leles, despite dec
T3805	22300-22301	VBP	denotes	e
T3806	22301-22304	NNS	denotes	les
T3807	22304-22306	,	denotes	,
T3808	22306-22307	NN	denotes	d
T3809	22307-22309	NNS	denotes	es
T3810	22309-22310	NN	denotes	p
T3811	22310-22312	IN	denotes	it
T3812	22312-22313	NNS	denotes	e
T3813	22314-22315	VBN	denotes	d
T3814	22315-22316	NNS	denotes	e
T3815	22316-22317	NNS	denotes	c
T3817	22317-22319	JJ	denotes	re
T3816	22317-22325	sentence	denotes	reased m
T3818	22319-22320	NN	denotes	a
T3819	22320-22321	RBS	denotes	s
T3820	22321-22322	NNS	denotes	e
T3821	22322-22323	CC	denotes	d
T3822	22324-22325	NNS	denotes	m
T3826	22325-22328	NN	denotes	RNA
T3823	22325-22458	sentence	denotes	RNA levels, ameliorated TTD symptoms by increasing overall TFIIH levels in compound heterozygous XpdTTD/ †XPCS and XpdTTD/ †XP cells.
T3825	22329-22335	NNS	denotes	levels
T3827	22335-22337	,	denotes	,
T3824	22337-22348	VBN	denotes	ameliorated
T3828	22349-22352	NN	denotes	TTD
T3829	22353-22361	NNS	denotes	symptoms
T3830	22362-22364	IN	denotes	by
T3831	22365-22375	VBG	denotes	increasing
T3833	22376-22383	JJ	denotes	overall
T3834	22384-22389	NN	denotes	TFIIH
T3832	22390-22396	NNS	denotes	levels
T3835	22397-22399	IN	denotes	in
T3836	22400-22408	NN	denotes	compound
T3838	22409-22421	JJ	denotes	heterozygous
T3839	22422-22428	NN	denotes	XpdTTD
T3841	22428-22429	HYPH	denotes	/
T3840	22429-22435	NN	denotes	†XPCS
T3842	22436-22439	CC	denotes	and
T3843	22440-22446	NN	denotes	XpdTTD
T3845	22446-22447	HYPH	denotes	/
T3844	22447-22451	NN	denotes	†XP
T3837	22452-22457	NNS	denotes	cells
T3846	22457-22458	.	denotes	.
T3847	22458-22680	sentence	denotes	Previously, using comparative immunohistochemistry, we and others have shown an up to 70% reduction of TFIIH levels in primary fibroblasts from patients with TTD compared with wt controls due to reduced stability [16,17].
T3848	22459-22469	RB	denotes	Previously
T3850	22469-22471	,	denotes	,
T3851	22471-22476	VBG	denotes	using
T3852	22477-22488	JJ	denotes	comparative
T3853	22489-22509	NN	denotes	immunohistochemistry
T3854	22509-22511	,	denotes	,
T3855	22511-22513	PRP	denotes	we
T3856	22514-22517	CC	denotes	and
T3857	22518-22524	NNS	denotes	others
T3858	22525-22529	VBP	denotes	have
T3849	22530-22535	VBN	denotes	shown
T3859	22536-22538	DT	denotes	an
T3861	22539-22541	IN	denotes	up
T3863	22542-22544	IN	denotes	to
T3862	22545-22547	CD	denotes	70
T3864	22547-22548	NN	denotes	%
T3860	22549-22558	NN	denotes	reduction
T3865	22559-22561	IN	denotes	of
T3866	22562-22567	NN	denotes	TFIIH
T3867	22568-22574	NNS	denotes	levels
T3868	22575-22577	IN	denotes	in
T3869	22578-22585	JJ	denotes	primary
T3870	22586-22597	NNS	denotes	fibroblasts
T3871	22598-22602	IN	denotes	from
T3872	22603-22611	NNS	denotes	patients
T3873	22612-22616	IN	denotes	with
T3874	22617-22620	NN	denotes	TTD
T3875	22621-22629	VBN	denotes	compared
T3876	22630-22634	IN	denotes	with
T3877	22635-22637	NN	denotes	wt
T3878	22638-22646	NNS	denotes	controls
T3879	22647-22650	IN	denotes	due
T3880	22651-22653	IN	denotes	to
T3881	22654-22661	VBN	denotes	reduced
T3882	22662-22671	NN	denotes	stability
T3883	22672-22673	-LRB-	denotes	[
T3885	22673-22675	CD	denotes	16
T3886	22675-22676	,	denotes	,
T3884	22676-22678	CD	denotes	17
T3887	22678-22679	-RRB-	denotes	]
T3888	22679-22680	.	denotes	.
T3889	22680-22934	sentence	denotes	Despite overexpression of mRNA from the XpdTTD allele relative to the wt allele (Figure 1E), TFIIH protein levels were reduced by 50% in primary mouse XpdTTD/TTD fibroblasts (Figure 4E and 4F), thereby mimicking the situation in human patients with TTD.
T3890	22681-22688	IN	denotes	Despite
T3892	22689-22703	NN	denotes	overexpression
T3893	22704-22706	IN	denotes	of
T3894	22707-22711	NN	denotes	mRNA
T3895	22712-22716	IN	denotes	from
T3896	22717-22720	DT	denotes	the
T3898	22721-22727	NN	denotes	XpdTTD
T3897	22728-22734	NN	denotes	allele
T3899	22735-22743	JJ	denotes	relative
T3900	22744-22746	IN	denotes	to
T3901	22747-22750	DT	denotes	the
T3903	22751-22753	NN	denotes	wt
T3902	22754-22760	NN	denotes	allele
T3904	22761-22762	-LRB-	denotes	(
T3906	22762-22768	NN	denotes	Figure
T3905	22769-22771	NN	denotes	1E
T3907	22771-22772	-RRB-	denotes	)
T3908	22772-22774	,	denotes	,
T3909	22774-22779	NN	denotes	TFIIH
T3911	22780-22787	NN	denotes	protein
T3910	22788-22794	NNS	denotes	levels
T3912	22795-22799	VBD	denotes	were
T3891	22800-22807	VBN	denotes	reduced
T3913	22808-22810	IN	denotes	by
T3914	22811-22813	CD	denotes	50
T3915	22813-22814	NN	denotes	%
T3916	22815-22817	IN	denotes	in
T3917	22818-22825	JJ	denotes	primary
T3919	22826-22831	NN	denotes	mouse
T3920	22832-22838	NN	denotes	XpdTTD
T3922	22838-22839	HYPH	denotes	/
T3921	22839-22842	NN	denotes	TTD
T3918	22843-22854	NNS	denotes	fibroblasts
T3923	22855-22856	-LRB-	denotes	(
T3925	22856-22862	NN	denotes	Figure
T3924	22863-22865	NN	denotes	4E
T3926	22866-22869	CC	denotes	and
T3927	22870-22872	NN	denotes	4F
T3928	22872-22873	-RRB-	denotes	)
T3929	22873-22875	,	denotes	,
T3930	22875-22882	RB	denotes	thereby
T3931	22883-22892	VBG	denotes	mimicking
T3932	22893-22896	DT	denotes	the
T3933	22897-22906	NN	denotes	situation
T3934	22907-22909	IN	denotes	in
T3935	22910-22915	JJ	denotes	human
T3936	22916-22924	NNS	denotes	patients
T3937	22925-22929	IN	denotes	with
T3938	22930-22933	NN	denotes	TTD
T3939	22933-22934	.	denotes	.
T3940	22934-23063	sentence	denotes	In accordance with the gene dosage, a further reduction of up to 70% of the wt level was observed in hemizygous XpdTTD/KO cells.
T3941	22935-22937	IN	denotes	In
T3943	22938-22948	NN	denotes	accordance
T3944	22949-22953	IN	denotes	with
T3945	22954-22957	DT	denotes	the
T3947	22958-22962	NN	denotes	gene
T3946	22963-22969	NN	denotes	dosage
T3948	22969-22971	,	denotes	,
T3949	22971-22972	DT	denotes	a
T3951	22973-22980	JJ	denotes	further
T3950	22981-22990	NN	denotes	reduction
T3952	22991-22993	IN	denotes	of
T3953	22994-22996	IN	denotes	up
T3955	22997-22999	IN	denotes	to
T3954	23000-23002	CD	denotes	70
T3956	23002-23003	NN	denotes	%
T3957	23004-23006	IN	denotes	of
T3958	23007-23010	DT	denotes	the
T3960	23011-23013	NN	denotes	wt
T3959	23014-23019	NN	denotes	level
T3961	23020-23023	VBD	denotes	was
T3942	23024-23032	VBN	denotes	observed
T3962	23033-23035	IN	denotes	in
T3963	23036-23046	JJ	denotes	hemizygous
T3965	23047-23053	NN	denotes	XpdTTD
T3967	23053-23054	HYPH	denotes	/
T3966	23054-23056	NN	denotes	KO
T3964	23057-23062	NNS	denotes	cells
T3968	23062-23063	.	denotes	.
T3969	23063-23257	sentence	denotes	Consistent with low mRNA expression levels, neither the Xpd†XPCS nor the Xpd†XP allele was able to restore TFIIH abundance to wt levels in XpdTTD compound heterozygote cells (Figure 4E and 4F).
T3970	23064-23074	JJ	denotes	Consistent
T3972	23075-23079	IN	denotes	with
T3973	23080-23083	JJ	denotes	low
T3975	23084-23088	NN	denotes	mRNA
T3976	23089-23099	NN	denotes	expression
T3974	23100-23106	NNS	denotes	levels
T3977	23106-23108	,	denotes	,
T3978	23108-23115	CC	denotes	neither
T3980	23116-23119	DT	denotes	the
T3981	23120-23128	NN	denotes	Xpd†XPCS
T3982	23129-23132	CC	denotes	nor
T3983	23133-23136	DT	denotes	the
T3984	23137-23143	NN	denotes	Xpd†XP
T3979	23144-23150	NN	denotes	allele
T3971	23151-23154	VBD	denotes	was
T3985	23155-23159	JJ	denotes	able
T3986	23160-23162	TO	denotes	to
T3987	23163-23170	VB	denotes	restore
T3988	23171-23176	NN	denotes	TFIIH
T3989	23177-23186	NN	denotes	abundance
T3990	23187-23189	IN	denotes	to
T3991	23190-23192	NN	denotes	wt
T3992	23193-23199	NNS	denotes	levels
T3993	23200-23202	IN	denotes	in
T3994	23203-23209	NN	denotes	XpdTTD
T3996	23210-23218	NN	denotes	compound
T3997	23219-23231	NN	denotes	heterozygote
T3995	23232-23237	NNS	denotes	cells
T3998	23238-23239	-LRB-	denotes	(
T4000	23239-23245	NN	denotes	Figure
T3999	23246-23248	NN	denotes	4E
T4001	23249-23252	CC	denotes	and
T4002	23253-23255	NN	denotes	4F
T4003	23255-23256	-RRB-	denotes	)
T4004	23256-23257	.	denotes	.
T4005	23257-23534	sentence	denotes	Thus, the improved UV survival observed in compound heterozygote cells (Figure 4A) and likely the rescue of TTD progeroid symptoms (Figure 3) were not due to normalisation of TFIIH levels, suggesting a qualitative rather than a quantitative effect on these phenotypes in vivo.
T4006	23258-23262	RB	denotes	Thus
T4008	23262-23264	,	denotes	,
T4009	23264-23267	DT	denotes	the
T4011	23268-23276	VBN	denotes	improved
T4012	23277-23279	NN	denotes	UV
T4010	23280-23288	NN	denotes	survival
T4013	23289-23297	VBN	denotes	observed
T4014	23298-23300	IN	denotes	in
T4015	23301-23309	NN	denotes	compound
T4017	23310-23322	NN	denotes	heterozygote
T4016	23323-23328	NNS	denotes	cells
T4018	23329-23330	-LRB-	denotes	(
T4020	23330-23336	NN	denotes	Figure
T4019	23337-23339	NN	denotes	4A
T4021	23339-23340	-RRB-	denotes	)
T4022	23341-23344	CC	denotes	and
T4023	23345-23351	RB	denotes	likely
T4025	23352-23355	DT	denotes	the
T4024	23356-23362	NN	denotes	rescue
T4026	23363-23365	IN	denotes	of
T4027	23366-23369	NN	denotes	TTD
T4029	23370-23379	NN	denotes	progeroid
T4028	23380-23388	NNS	denotes	symptoms
T4030	23389-23390	-LRB-	denotes	(
T4031	23390-23396	NN	denotes	Figure
T4032	23397-23398	CD	denotes	3
T4033	23398-23399	-RRB-	denotes	)
T4007	23400-23404	VBD	denotes	were
T4034	23405-23408	RB	denotes	not
T4035	23409-23412	IN	denotes	due
T4036	23413-23415	IN	denotes	to
T4037	23416-23429	NN	denotes	normalisation
T4038	23430-23432	IN	denotes	of
T4039	23433-23438	NN	denotes	TFIIH
T4040	23439-23445	NNS	denotes	levels
T4041	23445-23447	,	denotes	,
T4042	23447-23457	VBG	denotes	suggesting
T4043	23458-23459	DT	denotes	a
T4044	23460-23471	JJ	denotes	qualitative
T4046	23472-23478	RB	denotes	rather
T4047	23479-23483	IN	denotes	than
T4048	23484-23485	DT	denotes	a
T4049	23486-23498	JJ	denotes	quantitative
T4045	23499-23505	NN	denotes	effect
T4050	23506-23508	IN	denotes	on
T4051	23509-23514	DT	denotes	these
T4052	23515-23525	NNS	denotes	phenotypes
T4053	23526-23528	FW	denotes	in
T4054	23529-23533	FW	denotes	vivo
T4055	23533-23534	.	denotes	.
T4056	23534-23683	sentence	denotes	In contrast, the level of XPCS mRNA expression did affect the ability of the encoded protein (XPDG602D) to restore the TTD hair phenotype to normal.
T4057	23535-23537	IN	denotes	In
T4059	23538-23546	NN	denotes	contrast
T4060	23546-23548	,	denotes	,
T4061	23548-23551	DT	denotes	the
T4062	23552-23557	NN	denotes	level
T4063	23558-23560	IN	denotes	of
T4064	23561-23565	NN	denotes	XPCS
T4066	23566-23570	NN	denotes	mRNA
T4065	23571-23581	NN	denotes	expression
T4067	23582-23585	VBD	denotes	did
T4058	23586-23592	VB	denotes	affect
T4068	23593-23596	DT	denotes	the
T4069	23597-23604	NN	denotes	ability
T4070	23605-23607	IN	denotes	of
T4071	23608-23611	DT	denotes	the
T4073	23612-23619	VBN	denotes	encoded
T4072	23620-23627	NN	denotes	protein
T4074	23628-23629	-LRB-	denotes	(
T4075	23629-23637	NN	denotes	XPDG602D
T4076	23637-23638	-RRB-	denotes	)
T4077	23639-23641	TO	denotes	to
T4078	23642-23649	VB	denotes	restore
T4079	23650-23653	DT	denotes	the
T4081	23654-23657	NN	denotes	TTD
T4082	23658-23662	NN	denotes	hair
T4080	23663-23672	NN	denotes	phenotype
T4083	23673-23675	IN	denotes	to
T4084	23676-23682	JJ	denotes	normal
T4085	23682-23683	.	denotes	.
T4086	23683-23946	sentence	denotes	Notably, XpdTTD/ †XPCS animals had a partial TTD hair phenotype, correlating with low levels of Xpd†XPCS expression, whereas XpdTTD/XPCS animals had wt hair, correlating with normal expression levels from the viable XpdXPCS allele (Table 2 and unpublished data).
T4087	23684-23691	RB	denotes	Notably
T4089	23691-23693	,	denotes	,
T4090	23693-23699	NN	denotes	XpdTTD
T4092	23699-23700	HYPH	denotes	/
T4091	23700-23706	NN	denotes	†XPCS
T4093	23707-23714	NNS	denotes	animals
T4088	23715-23718	VBD	denotes	had
T4094	23719-23720	DT	denotes	a
T4096	23721-23728	JJ	denotes	partial
T4097	23729-23732	NN	denotes	TTD
T4098	23733-23737	NN	denotes	hair
T4095	23738-23747	NN	denotes	phenotype
T4099	23747-23749	,	denotes	,
T4100	23749-23760	VBG	denotes	correlating
T4101	23761-23765	IN	denotes	with
T4102	23766-23769	JJ	denotes	low
T4103	23770-23776	NNS	denotes	levels
T4104	23777-23779	IN	denotes	of
T4105	23780-23788	NN	denotes	Xpd†XPCS
T4106	23789-23799	NN	denotes	expression
T4107	23799-23801	,	denotes	,
T4108	23801-23808	IN	denotes	whereas
T4110	23809-23815	NN	denotes	XpdTTD
T4112	23815-23816	HYPH	denotes	/
T4111	23816-23820	NN	denotes	XPCS
T4113	23821-23828	NNS	denotes	animals
T4109	23829-23832	VBD	denotes	had
T4114	23833-23835	NN	denotes	wt
T4115	23836-23840	NN	denotes	hair
T4116	23840-23842	,	denotes	,
T4117	23842-23853	VBG	denotes	correlating
T4118	23854-23858	IN	denotes	with
T4119	23859-23865	JJ	denotes	normal
T4121	23866-23876	NN	denotes	expression
T4120	23877-23883	NNS	denotes	levels
T4122	23884-23888	IN	denotes	from
T4123	23889-23892	DT	denotes	the
T4125	23893-23899	JJ	denotes	viable
T4126	23900-23907	NN	denotes	XpdXPCS
T4124	23908-23914	NN	denotes	allele
T4127	23915-23916	-LRB-	denotes	(
T4128	23916-23921	NN	denotes	Table
T4129	23922-23923	CD	denotes	2
T4130	23924-23927	CC	denotes	and
T4131	23928-23939	JJ	denotes	unpublished
T4132	23940-23944	NNS	denotes	data
T4133	23944-23945	-RRB-	denotes	)
T4134	23945-23946	.	denotes	.
T4135	23946-24074	sentence	denotes	Thus, the range of expression levels from these two mutant alleles affected their ability to complement some phenotypes (hair).
T4136	23947-23951	RB	denotes	Thus
T4138	23951-23953	,	denotes	,
T4139	23953-23956	DT	denotes	the
T4140	23957-23962	NN	denotes	range
T4141	23963-23965	IN	denotes	of
T4142	23966-23976	NN	denotes	expression
T4143	23977-23983	NNS	denotes	levels
T4144	23984-23988	IN	denotes	from
T4145	23989-23994	DT	denotes	these
T4147	23995-23998	CD	denotes	two
T4148	23999-24005	JJ	denotes	mutant
T4146	24006-24013	NNS	denotes	alleles
T4137	24014-24022	VBD	denotes	affected
T4149	24023-24028	PRP$	denotes	their
T4150	24029-24036	NN	denotes	ability
T4151	24037-24039	TO	denotes	to
T4152	24040-24050	VB	denotes	complement
T4153	24051-24055	DT	denotes	some
T4154	24056-24066	NNS	denotes	phenotypes
T4155	24067-24068	-LRB-	denotes	(
T4156	24068-24072	NN	denotes	hair
T4157	24072-24073	-RRB-	denotes	)
T4158	24073-24074	.	denotes	.
T4159	24074-24237	sentence	denotes	An overview of the functional relationships between Xpd alleles, phenotypes, and the presumed underlying TFIIH function in mice and cells is presented in Table 2.
T4160	24075-24077	DT	denotes	An
T4161	24078-24086	NN	denotes	overview
T4163	24087-24089	IN	denotes	of
T4164	24090-24093	DT	denotes	the
T4166	24094-24104	JJ	denotes	functional
T4165	24105-24118	NNS	denotes	relationships
T4167	24119-24126	IN	denotes	between
T4168	24127-24130	NN	denotes	Xpd
T4169	24131-24138	NNS	denotes	alleles
T4170	24138-24140	,	denotes	,
T4171	24140-24150	NNS	denotes	phenotypes
T4172	24150-24152	,	denotes	,
T4173	24152-24155	CC	denotes	and
T4174	24156-24159	DT	denotes	the
T4176	24160-24168	VBN	denotes	presumed
T4177	24169-24179	VBG	denotes	underlying
T4178	24180-24185	NN	denotes	TFIIH
T4175	24186-24194	NN	denotes	function
T4179	24195-24197	IN	denotes	in
T4180	24198-24202	NNS	denotes	mice
T4181	24203-24206	CC	denotes	and
T4182	24207-24212	NNS	denotes	cells
T4183	24213-24215	VBZ	denotes	is
T4162	24216-24225	VBN	denotes	presented
T4184	24226-24228	IN	denotes	in
T4185	24229-24234	NN	denotes	Table
T4186	24235-24236	CD	denotes	2
T4187	24236-24237	.	denotes	.
T4259	24251-24261	NN	denotes	Dissection
T4260	24262-24264	IN	denotes	of
T4261	24265-24274	JJ	denotes	Biallelic
T4262	24275-24282	NNS	denotes	Effects
T4263	24283-24287	IN	denotes	from
T4264	24288-24293	JJ	denotes	other
T4265	24294-24306	NNS	denotes	Determinants
T4266	24307-24309	IN	denotes	of
T4267	24310-24319	NN	denotes	Phenotype
T4268	24319-24611	sentence	denotes	Although phenotypic consequences, referred to here as biallelic effects, resulting from two different mutant alleles in compound heterozygote patients have been postulated, such effects have historically been difficult to distinguish from the influence of environment and genetic background.
T4269	24320-24328	IN	denotes	Although
T4271	24329-24339	JJ	denotes	phenotypic
T4272	24340-24352	NNS	denotes	consequences
T4273	24352-24354	,	denotes	,
T4274	24354-24362	VBN	denotes	referred
T4275	24363-24365	IN	denotes	to
T4276	24366-24370	RB	denotes	here
T4277	24371-24373	IN	denotes	as
T4278	24374-24383	JJ	denotes	biallelic
T4279	24384-24391	NNS	denotes	effects
T4280	24391-24393	,	denotes	,
T4281	24393-24402	VBG	denotes	resulting
T4282	24403-24407	IN	denotes	from
T4283	24408-24411	CD	denotes	two
T4285	24412-24421	JJ	denotes	different
T4286	24422-24428	JJ	denotes	mutant
T4284	24429-24436	NNS	denotes	alleles
T4287	24437-24439	IN	denotes	in
T4288	24440-24448	NN	denotes	compound
T4290	24449-24461	NN	denotes	heterozygote
T4289	24462-24470	NNS	denotes	patients
T4291	24471-24475	VBP	denotes	have
T4292	24476-24480	VBN	denotes	been
T4270	24481-24491	VBN	denotes	postulated
T4294	24491-24493	,	denotes	,
T4295	24493-24497	JJ	denotes	such
T4296	24498-24505	NNS	denotes	effects
T4297	24506-24510	VBP	denotes	have
T4298	24511-24523	RB	denotes	historically
T4293	24524-24528	VBN	denotes	been
T4299	24529-24538	JJ	denotes	difficult
T4300	24539-24541	TO	denotes	to
T4301	24542-24553	VB	denotes	distinguish
T4302	24554-24558	IN	denotes	from
T4303	24559-24562	DT	denotes	the
T4304	24563-24572	NN	denotes	influence
T4305	24573-24575	IN	denotes	of
T4306	24576-24587	NN	denotes	environment
T4307	24588-24591	CC	denotes	and
T4308	24592-24599	JJ	denotes	genetic
T4309	24600-24610	NN	denotes	background
T4310	24610-24611	.	denotes	.
T4311	24611-24816	sentence	denotes	We used a genetically defined mammalian model system under controlled environmental conditions to reveal phenotypic effects attributable specifically to combinations of differentially mutated Xpd alleles.
T4312	24612-24614	PRP	denotes	We
T4313	24615-24619	VBD	denotes	used
T4314	24620-24621	DT	denotes	a
T4316	24622-24633	RB	denotes	genetically
T4317	24634-24641	VBN	denotes	defined
T4318	24642-24651	JJ	denotes	mammalian
T4319	24652-24657	NN	denotes	model
T4315	24658-24664	NN	denotes	system
T4320	24665-24670	IN	denotes	under
T4321	24671-24681	JJ	denotes	controlled
T4323	24682-24695	JJ	denotes	environmental
T4322	24696-24706	NNS	denotes	conditions
T4324	24707-24709	TO	denotes	to
T4325	24710-24716	VB	denotes	reveal
T4326	24717-24727	JJ	denotes	phenotypic
T4327	24728-24735	NNS	denotes	effects
T4328	24736-24748	JJ	denotes	attributable
T4329	24749-24761	RB	denotes	specifically
T4330	24762-24764	IN	denotes	to
T4331	24765-24777	NNS	denotes	combinations
T4332	24778-24780	IN	denotes	of
T4333	24781-24795	RB	denotes	differentially
T4334	24796-24803	VBN	denotes	mutated
T4336	24804-24807	NN	denotes	Xpd
T4335	24808-24815	NNS	denotes	alleles
T4337	24815-24816	.	denotes	.
T4338	24816-24876	sentence	denotes	The observed biallelic effects were of three general types.
T4339	24817-24820	DT	denotes	The
T4341	24821-24829	VBN	denotes	observed
T4342	24830-24839	JJ	denotes	biallelic
T4340	24840-24847	NNS	denotes	effects
T4343	24848-24852	VBD	denotes	were
T4344	24853-24855	IN	denotes	of
T4345	24856-24861	CD	denotes	three
T4347	24862-24869	JJ	denotes	general
T4346	24870-24875	NNS	denotes	types
T4348	24875-24876	.	denotes	.
T4349	24876-25064	sentence	denotes	In the first, the allele associated in a homozygous state with a phenotype closer to wt singularly determined the phenotypic outcome, a phenomenon widely known in human recessive disease.
T4350	24877-24879	IN	denotes	In
T4352	24880-24883	DT	denotes	the
T4353	24884-24889	JJ	denotes	first
T4354	24889-24891	,	denotes	,
T4355	24891-24894	DT	denotes	the
T4356	24895-24901	NN	denotes	allele
T4357	24902-24912	VBN	denotes	associated
T4358	24913-24915	IN	denotes	in
T4359	24916-24917	DT	denotes	a
T4361	24918-24928	JJ	denotes	homozygous
T4360	24929-24934	NN	denotes	state
T4362	24935-24939	IN	denotes	with
T4363	24940-24941	DT	denotes	a
T4364	24942-24951	NN	denotes	phenotype
T4365	24952-24958	RBR	denotes	closer
T4366	24959-24961	IN	denotes	to
T4367	24962-24964	NN	denotes	wt
T4368	24965-24975	RB	denotes	singularly
T4351	24976-24986	VBN	denotes	determined
T4369	24987-24990	DT	denotes	the
T4371	24991-25001	JJ	denotes	phenotypic
T4370	25002-25009	NN	denotes	outcome
T4372	25009-25011	,	denotes	,
T4373	25011-25012	DT	denotes	a
T4374	25013-25023	NN	denotes	phenomenon
T4375	25024-25030	RB	denotes	widely
T4376	25031-25036	VBN	denotes	known
T4377	25037-25039	IN	denotes	in
T4378	25040-25045	JJ	denotes	human
T4380	25046-25055	JJ	denotes	recessive
T4379	25056-25063	NN	denotes	disease
T4381	25063-25064	.	denotes	.
T4382	25064-25195	sentence	denotes	Because these Xpd alleles functioned at or near wt levels with respect to a particular function, we call these effects “dominant”.
T4383	25065-25072	IN	denotes	Because
T4385	25073-25078	DT	denotes	these
T4387	25079-25082	NN	denotes	Xpd
T4386	25083-25090	NNS	denotes	alleles
T4384	25091-25101	VBD	denotes	functioned
T4389	25102-25104	IN	denotes	at
T4390	25105-25107	CC	denotes	or
T4391	25108-25112	IN	denotes	near
T4392	25113-25115	NN	denotes	wt
T4393	25116-25122	NNS	denotes	levels
T4394	25123-25127	IN	denotes	with
T4395	25128-25135	NN	denotes	respect
T4396	25136-25138	IN	denotes	to
T4397	25139-25140	DT	denotes	a
T4399	25141-25151	JJ	denotes	particular
T4398	25152-25160	NN	denotes	function
T4400	25160-25162	,	denotes	,
T4401	25162-25164	PRP	denotes	we
T4388	25165-25169	VBP	denotes	call
T4402	25170-25175	DT	denotes	these
T4403	25176-25183	NNS	denotes	effects
T4404	25184-25185	``	denotes	“
T4405	25185-25193	JJ	denotes	dominant
T4406	25193-25194	''	denotes	”
T4407	25194-25195	.	denotes	.
T4408	25195-25364	sentence	denotes	Such alleles can also be referred to as “separation of function” alleles, because they allow dissection of the roles of multifunctional proteins in specific phenotypes.
T4409	25196-25200	JJ	denotes	Such
T4410	25201-25208	NNS	denotes	alleles
T4412	25209-25212	MD	denotes	can
T4413	25213-25217	RB	denotes	also
T4414	25218-25220	VB	denotes	be
T4411	25221-25229	VBN	denotes	referred
T4415	25230-25232	IN	denotes	to
T4416	25233-25235	IN	denotes	as
T4417	25236-25237	``	denotes	“
T4419	25237-25247	NN	denotes	separation
T4420	25248-25250	IN	denotes	of
T4421	25251-25259	NN	denotes	function
T4422	25259-25260	''	denotes	”
T4418	25261-25268	NNS	denotes	alleles
T4423	25268-25270	,	denotes	,
T4424	25270-25277	IN	denotes	because
T4426	25278-25282	PRP	denotes	they
T4425	25283-25288	VBP	denotes	allow
T4427	25289-25299	NN	denotes	dissection
T4428	25300-25302	IN	denotes	of
T4429	25303-25306	DT	denotes	the
T4430	25307-25312	NNS	denotes	roles
T4431	25313-25315	IN	denotes	of
T4432	25316-25331	JJ	denotes	multifunctional
T4433	25332-25340	NN	denotes	proteins
T4434	25341-25343	IN	denotes	in
T4435	25344-25352	JJ	denotes	specific
T4436	25353-25363	NNS	denotes	phenotypes
T4437	25363-25364	.	denotes	.
T4438	25364-25741	sentence	denotes	Secondly, highlighting the potential relevance of current findings to all diploid organisms including humans was the observation that in one compound heterozygous animal, the Xpd allelic relationship could shift from A dominant \|a recessive to A recessive \|a dominant with respect to different phenotypes in a time-dependent and tissue-specific manner (see below and Table 2).
T4439	25365-25373	RB	denotes	Secondly
T4441	25373-25375	,	denotes	,
T4442	25375-25387	VBG	denotes	highlighting
T4443	25388-25391	DT	denotes	the
T4445	25392-25401	JJ	denotes	potential
T4444	25402-25411	NN	denotes	relevance
T4446	25412-25414	IN	denotes	of
T4447	25415-25422	JJ	denotes	current
T4448	25423-25431	NNS	denotes	findings
T4449	25432-25434	IN	denotes	to
T4450	25435-25438	DT	denotes	all
T4452	25439-25446	JJ	denotes	diploid
T4451	25447-25456	NNS	denotes	organisms
T4453	25457-25466	VBG	denotes	including
T4454	25467-25473	NNS	denotes	humans
T4440	25474-25477	VBD	denotes	was
T4455	25478-25481	DT	denotes	the
T4456	25482-25493	NN	denotes	observation
T4457	25494-25498	IN	denotes	that
T4459	25499-25501	IN	denotes	in
T4460	25502-25505	CD	denotes	one
T4462	25506-25514	NN	denotes	compound
T4463	25515-25527	JJ	denotes	heterozygous
T4461	25528-25534	NN	denotes	animal
T4464	25534-25536	,	denotes	,
T4465	25536-25539	DT	denotes	the
T4467	25540-25543	NN	denotes	Xpd
T4468	25544-25551	JJ	denotes	allelic
T4466	25552-25564	NN	denotes	relationship
T4469	25565-25570	MD	denotes	could
T4458	25571-25576	VB	denotes	shift
T4470	25577-25581	IN	denotes	from
T4471	25582-25592	JJ	denotes	A dominant
T4473	25593-25594	HYPH	denotes	\|
T4472	25594-25605	JJ	denotes	a recessive
T4474	25606-25608	IN	denotes	to
T4475	25609-25620	JJ	denotes	A recessive
T4477	25621-25622	HYPH	denotes	\|
T4476	25622-25632	JJ	denotes	a dominant
T4478	25633-25637	IN	denotes	with
T4479	25638-25645	NN	denotes	respect
T4480	25646-25648	IN	denotes	to
T4481	25649-25658	JJ	denotes	different
T4482	25659-25669	NNS	denotes	phenotypes
T4483	25670-25672	IN	denotes	in
T4484	25673-25674	DT	denotes	a
T4486	25675-25679	NN	denotes	time
T4488	25679-25680	HYPH	denotes	-
T4487	25680-25689	JJ	denotes	dependent
T4489	25690-25693	CC	denotes	and
T4490	25694-25700	NN	denotes	tissue
T4492	25700-25701	HYPH	denotes	-
T4491	25701-25709	JJ	denotes	specific
T4485	25710-25716	NN	denotes	manner
T4493	25717-25718	-LRB-	denotes	(
T4494	25718-25721	VB	denotes	see
T4495	25722-25727	RB	denotes	below
T4497	25728-25731	CC	denotes	and
T4496	25732-25737	NN	denotes	Table
T4498	25738-25739	CD	denotes	2
T4499	25739-25740	-RRB-	denotes	)
T4500	25740-25741	.	denotes	.
T4501	25741-25928	sentence	denotes	In the third type of biallelic effect, known as interallelic complementation, two mutant alleles produced a phenotype closer to wt than either could alone in a homo- or hemizygous state.
T4502	25742-25744	IN	denotes	In
T4504	25745-25748	DT	denotes	the
T4506	25749-25754	JJ	denotes	third
T4505	25755-25759	NN	denotes	type
T4507	25760-25762	IN	denotes	of
T4508	25763-25772	JJ	denotes	biallelic
T4509	25773-25779	NN	denotes	effect
T4510	25779-25781	,	denotes	,
T4511	25781-25786	VBN	denotes	known
T4512	25787-25789	IN	denotes	as
T4513	25790-25802	JJ	denotes	interallelic
T4514	25803-25818	NN	denotes	complementation
T4515	25818-25820	,	denotes	,
T4516	25820-25823	CD	denotes	two
T4518	25824-25830	JJ	denotes	mutant
T4517	25831-25838	NNS	denotes	alleles
T4503	25839-25847	VBD	denotes	produced
T4519	25848-25849	DT	denotes	a
T4520	25850-25859	NN	denotes	phenotype
T4521	25860-25866	RBR	denotes	closer
T4522	25867-25869	IN	denotes	to
T4523	25870-25872	NN	denotes	wt
T4524	25873-25877	IN	denotes	than
T4526	25878-25884	DT	denotes	either
T4527	25885-25890	MD	denotes	could
T4525	25891-25896	RB	denotes	alone
T4528	25897-25899	IN	denotes	in
T4529	25900-25901	DT	denotes	a
T4531	25902-25906	AFX	denotes	homo
T4533	25906-25907	HYPH	denotes	-
T4534	25908-25910	CC	denotes	or
T4532	25911-25921	JJ	denotes	hemizygous
T4530	25922-25927	NN	denotes	state
T4535	25927-25928	.	denotes	.
T4536	25928-26103	sentence	denotes	As summarised in Table 2, examples of all types of biallelic effects were observed in a variety of Xpd-associated phenotypes, ranging from brittle hair to segmental progeria.
T4537	25929-25931	IN	denotes	As
T4538	25932-25942	VBN	denotes	summarised
T4540	25943-25945	IN	denotes	in
T4541	25946-25951	NN	denotes	Table
T4542	25952-25953	CD	denotes	2
T4543	25953-25955	,	denotes	,
T4544	25955-25963	NNS	denotes	examples
T4545	25964-25966	IN	denotes	of
T4546	25967-25970	DT	denotes	all
T4547	25971-25976	NNS	denotes	types
T4548	25977-25979	IN	denotes	of
T4549	25980-25989	JJ	denotes	biallelic
T4550	25990-25997	NNS	denotes	effects
T4551	25998-26002	VBD	denotes	were
T4539	26003-26011	VBN	denotes	observed
T4552	26012-26014	IN	denotes	in
T4553	26015-26016	DT	denotes	a
T4554	26017-26024	NN	denotes	variety
T4555	26025-26027	IN	denotes	of
T4556	26028-26031	NN	denotes	Xpd
T4558	26031-26032	HYPH	denotes	-
T4557	26032-26042	VBN	denotes	associated
T4559	26043-26053	NNS	denotes	phenotypes
T4560	26053-26055	,	denotes	,
T4561	26055-26062	VBG	denotes	ranging
T4562	26063-26067	IN	denotes	from
T4563	26068-26075	JJ	denotes	brittle
T4564	26076-26080	NN	denotes	hair
T4565	26081-26083	IN	denotes	to
T4566	26084-26093	JJ	denotes	segmental
T4567	26094-26102	NN	denotes	progeria
T4568	26102-26103	.	denotes	.
T4805	26105-26110	NN	denotes	TFIIH
T4806	26111-26113	IN	denotes	in
T4807	26114-26127	NN	denotes	Transcription
T4808	26128-26131	CC	denotes	and
T4809	26132-26138	NN	denotes	Repair
T4810	26138-26140	:	denotes	:
T4811	26140-26150	NNS	denotes	Mechanisms
T4812	26151-26153	IN	denotes	of
T4813	26154-26157	NN	denotes	XPD
T4815	26158-26165	NN	denotes	Disease
T4814	26166-26176	NN	denotes	Pleiotropy
T4816	26176-26466	sentence	denotes	We observed differences in the ability of XpdTTD versus homozygous lethal Xpd†XPCS and Xpd†XP alleles to function in two transcription-related phenotypes separated in the organism by both time and space: embryonic lethality and terminal differentiation of enucleating skin and blood cells.
T4817	26177-26179	PRP	denotes	We
T4818	26180-26188	VBD	denotes	observed
T4819	26189-26200	NNS	denotes	differences
T4820	26201-26203	IN	denotes	in
T4821	26204-26207	DT	denotes	the
T4822	26208-26215	NN	denotes	ability
T4823	26216-26218	IN	denotes	of
T4824	26219-26225	NN	denotes	XpdTTD
T4825	26226-26232	CC	denotes	versus
T4826	26233-26243	JJ	denotes	homozygous
T4828	26244-26250	JJ	denotes	lethal
T4829	26251-26259	NN	denotes	Xpd†XPCS
T4830	26260-26263	CC	denotes	and
T4831	26264-26270	NN	denotes	Xpd†XP
T4827	26271-26278	NNS	denotes	alleles
T4832	26279-26281	TO	denotes	to
T4833	26282-26290	VB	denotes	function
T4834	26291-26293	IN	denotes	in
T4835	26294-26297	CD	denotes	two
T4837	26298-26311	NN	denotes	transcription
T4839	26311-26312	HYPH	denotes	-
T4838	26312-26319	VBN	denotes	related
T4836	26320-26330	NNS	denotes	phenotypes
T4840	26331-26340	VBN	denotes	separated
T4841	26341-26343	IN	denotes	in
T4842	26344-26347	DT	denotes	the
T4843	26348-26356	NN	denotes	organism
T4844	26357-26359	IN	denotes	by
T4845	26360-26364	CC	denotes	both
T4846	26365-26369	NN	denotes	time
T4847	26370-26373	CC	denotes	and
T4848	26374-26379	NN	denotes	space
T4849	26379-26381	:	denotes	:
T4850	26381-26390	JJ	denotes	embryonic
T4851	26391-26400	NN	denotes	lethality
T4852	26401-26404	CC	denotes	and
T4853	26405-26413	JJ	denotes	terminal
T4854	26414-26429	NN	denotes	differentiation
T4855	26430-26432	IN	denotes	of
T4856	26433-26444	VBG	denotes	enucleating
T4857	26445-26449	NN	denotes	skin
T4858	26450-26453	CC	denotes	and
T4859	26454-26459	NN	denotes	blood
T4860	26460-26465	NNS	denotes	cells
T4861	26465-26466	.	denotes	.
T4862	26466-26646	sentence	denotes	The preblastocyst-stage homozygous lethality shared by the XpdKO, Xpd†XPCS, and Xpd†XP alleles most likely reflects a defect in basal transcription that is incompatible with life.
T4863	26467-26470	DT	denotes	The
T4865	26471-26484	NN	denotes	preblastocyst
T4867	26484-26485	HYPH	denotes	-
T4866	26485-26490	NN	denotes	stage
T4868	26491-26501	JJ	denotes	homozygous
T4864	26502-26511	NN	denotes	lethality
T4870	26512-26518	VBN	denotes	shared
T4871	26519-26521	IN	denotes	by
T4872	26522-26525	DT	denotes	the
T4874	26526-26531	NN	denotes	XpdKO
T4875	26531-26533	,	denotes	,
T4876	26533-26541	NN	denotes	Xpd†XPCS
T4877	26541-26543	,	denotes	,
T4878	26543-26546	CC	denotes	and
T4879	26547-26553	NN	denotes	Xpd†XP
T4873	26554-26561	NNS	denotes	alleles
T4880	26562-26566	RBS	denotes	most
T4881	26567-26573	RB	denotes	likely
T4869	26574-26582	VBZ	denotes	reflects
T4882	26583-26584	DT	denotes	a
T4883	26585-26591	NN	denotes	defect
T4884	26592-26594	IN	denotes	in
T4885	26595-26600	JJ	denotes	basal
T4886	26601-26614	NN	denotes	transcription
T4887	26615-26619	WDT	denotes	that
T4888	26620-26622	VBZ	denotes	is
T4889	26623-26635	JJ	denotes	incompatible
T4890	26636-26640	IN	denotes	with
T4891	26641-26645	NN	denotes	life
T4892	26645-26646	.	denotes	.
T4893	26646-26767	sentence	denotes	In XpdTTD/ †XPCS and XpdTTD/ †XP compound heterozygous mice, embryonic lethality was fully rescued by the XpdTTD allele.
T4894	26647-26649	IN	denotes	In
T4896	26650-26656	NN	denotes	XpdTTD
T4898	26656-26657	HYPH	denotes	/
T4897	26657-26663	NN	denotes	†XPCS
T4900	26664-26667	CC	denotes	and
T4901	26668-26674	NN	denotes	XpdTTD
T4903	26674-26675	HYPH	denotes	/
T4902	26675-26679	NN	denotes	†XP
T4904	26680-26688	NN	denotes	compound
T4905	26689-26701	JJ	denotes	heterozygous
T4899	26702-26706	NNS	denotes	mice
T4906	26706-26708	,	denotes	,
T4907	26708-26717	JJ	denotes	embryonic
T4908	26718-26727	NN	denotes	lethality
T4909	26728-26731	VBD	denotes	was
T4910	26732-26737	RB	denotes	fully
T4895	26738-26745	VBN	denotes	rescued
T4911	26746-26748	IN	denotes	by
T4912	26749-26752	DT	denotes	the
T4914	26753-26759	NN	denotes	XpdTTD
T4913	26760-26766	NN	denotes	allele
T4915	26766-26767	.	denotes	.
T4916	26767-27032	sentence	denotes	Because embryonic lethality was also fully rescued in XpdTTD/KO hemizygous mice, the XpdTTD allele can be considered as wt and thus dominant to each of the homozygous lethal alleles (XpdKO, Xpd†XPCS, and Xpd†XP) with respect to this particular phenotype (Table 2).
T4917	26768-26775	IN	denotes	Because
T4919	26776-26785	JJ	denotes	embryonic
T4920	26786-26795	NN	denotes	lethality
T4921	26796-26799	VBD	denotes	was
T4922	26800-26804	RB	denotes	also
T4923	26805-26810	RB	denotes	fully
T4918	26811-26818	VBN	denotes	rescued
T4925	26819-26821	IN	denotes	in
T4926	26822-26828	NN	denotes	XpdTTD
T4928	26828-26829	HYPH	denotes	/
T4927	26829-26831	NN	denotes	KO
T4930	26832-26842	JJ	denotes	hemizygous
T4929	26843-26847	NNS	denotes	mice
T4931	26847-26849	,	denotes	,
T4932	26849-26852	DT	denotes	the
T4934	26853-26859	NN	denotes	XpdTTD
T4933	26860-26866	NN	denotes	allele
T4935	26867-26870	MD	denotes	can
T4936	26871-26873	VB	denotes	be
T4924	26874-26884	VBN	denotes	considered
T4937	26885-26887	IN	denotes	as
T4938	26888-26890	NN	denotes	wt
T4939	26891-26894	CC	denotes	and
T4940	26895-26899	RB	denotes	thus
T4941	26900-26908	JJ	denotes	dominant
T4942	26909-26911	IN	denotes	to
T4943	26912-26916	DT	denotes	each
T4944	26917-26919	IN	denotes	of
T4945	26920-26923	DT	denotes	the
T4947	26924-26934	JJ	denotes	homozygous
T4948	26935-26941	JJ	denotes	lethal
T4946	26942-26949	NNS	denotes	alleles
T4949	26950-26951	-LRB-	denotes	(
T4950	26951-26956	NN	denotes	XpdKO
T4951	26956-26958	,	denotes	,
T4952	26958-26966	NN	denotes	Xpd†XPCS
T4953	26966-26968	,	denotes	,
T4954	26968-26971	CC	denotes	and
T4955	26972-26978	NN	denotes	Xpd†XP
T4956	26978-26979	-RRB-	denotes	)
T4957	26980-26984	IN	denotes	with
T4958	26985-26992	NN	denotes	respect
T4959	26993-26995	IN	denotes	to
T4960	26996-27000	DT	denotes	this
T4962	27001-27011	JJ	denotes	particular
T4961	27012-27021	NN	denotes	phenotype
T4963	27022-27023	-LRB-	denotes	(
T4964	27023-27028	NN	denotes	Table
T4965	27029-27030	CD	denotes	2
T4966	27030-27031	-RRB-	denotes	)
T4967	27031-27032	.	denotes	.
T4968	27032-27292	sentence	denotes	TTD-specific cutaneous and anaemic features, on the other hand, are thought to result from a specific kind of transcriptional insufficiency caused by depletion of unstable TFIIH during the terminal differentiation of skin, hair-shaft, and blood cells [16,24].
T4969	27033-27036	NN	denotes	TTD
T4971	27036-27037	HYPH	denotes	-
T4970	27037-27045	JJ	denotes	specific
T4973	27046-27055	JJ	denotes	cutaneous
T4974	27056-27059	CC	denotes	and
T4975	27060-27067	JJ	denotes	anaemic
T4972	27068-27076	NNS	denotes	features
T4977	27076-27078	,	denotes	,
T4978	27078-27080	IN	denotes	on
T4979	27081-27084	DT	denotes	the
T4981	27085-27090	JJ	denotes	other
T4980	27091-27095	NN	denotes	hand
T4982	27095-27097	,	denotes	,
T4983	27097-27100	VBP	denotes	are
T4976	27101-27108	VBN	denotes	thought
T4984	27109-27111	TO	denotes	to
T4985	27112-27118	VB	denotes	result
T4986	27119-27123	IN	denotes	from
T4987	27124-27125	DT	denotes	a
T4989	27126-27134	JJ	denotes	specific
T4988	27135-27139	NN	denotes	kind
T4990	27140-27142	IN	denotes	of
T4991	27143-27158	JJ	denotes	transcriptional
T4992	27159-27172	NN	denotes	insufficiency
T4993	27173-27179	VBN	denotes	caused
T4994	27180-27182	IN	denotes	by
T4995	27183-27192	NN	denotes	depletion
T4996	27193-27195	IN	denotes	of
T4997	27196-27204	JJ	denotes	unstable
T4998	27205-27210	NN	denotes	TFIIH
T4999	27211-27217	IN	denotes	during
T5000	27218-27221	DT	denotes	the
T5002	27222-27230	JJ	denotes	terminal
T5001	27231-27246	NN	denotes	differentiation
T5003	27247-27249	IN	denotes	of
T5004	27250-27254	NN	denotes	skin
T5006	27254-27256	,	denotes	,
T5007	27256-27260	NN	denotes	hair
T5009	27260-27261	HYPH	denotes	-
T5008	27261-27266	NN	denotes	shaft
T5010	27266-27268	,	denotes	,
T5011	27268-27271	CC	denotes	and
T5012	27272-27277	NN	denotes	blood
T5005	27278-27283	NNS	denotes	cells
T5013	27284-27285	-LRB-	denotes	[
T5015	27285-27287	CD	denotes	16
T5016	27287-27288	,	denotes	,
T5014	27288-27290	CD	denotes	24
T5017	27290-27291	-RRB-	denotes	]
T5018	27291-27292	.	denotes	.
T5019	27292-27537	sentence	denotes	In compound heterozygous mice, both homozygous lethal Xpd†XPCS and Xpd†XP alleles were able to alleviate XpdTTD-specific cutaneous and anaemic features and can thus be defined as dominant over the XpdTTD allele with respect to these phenotypes.
T5020	27293-27295	IN	denotes	In
T5022	27296-27304	NN	denotes	compound
T5024	27305-27317	JJ	denotes	heterozygous
T5023	27318-27322	NNS	denotes	mice
T5025	27322-27324	,	denotes	,
T5026	27324-27328	DT	denotes	both
T5028	27329-27339	JJ	denotes	homozygous
T5029	27340-27346	JJ	denotes	lethal
T5030	27347-27355	NN	denotes	Xpd†XPCS
T5031	27356-27359	CC	denotes	and
T5032	27360-27366	NN	denotes	Xpd†XP
T5027	27367-27374	NNS	denotes	alleles
T5021	27375-27379	VBD	denotes	were
T5033	27380-27384	JJ	denotes	able
T5034	27385-27387	TO	denotes	to
T5035	27388-27397	VB	denotes	alleviate
T5036	27398-27404	NN	denotes	XpdTTD
T5038	27404-27405	HYPH	denotes	-
T5037	27405-27413	JJ	denotes	specific
T5040	27414-27423	JJ	denotes	cutaneous
T5041	27424-27427	CC	denotes	and
T5042	27428-27435	JJ	denotes	anaemic
T5039	27436-27444	NNS	denotes	features
T5043	27445-27448	CC	denotes	and
T5044	27449-27452	MD	denotes	can
T5046	27453-27457	RB	denotes	thus
T5047	27458-27460	VB	denotes	be
T5045	27461-27468	VBN	denotes	defined
T5048	27469-27471	IN	denotes	as
T5049	27472-27480	JJ	denotes	dominant
T5050	27481-27485	IN	denotes	over
T5051	27486-27489	DT	denotes	the
T5053	27490-27496	NN	denotes	XpdTTD
T5052	27497-27503	NN	denotes	allele
T5054	27504-27508	IN	denotes	with
T5055	27509-27516	NN	denotes	respect
T5056	27517-27519	IN	denotes	to
T5057	27520-27525	DT	denotes	these
T5058	27526-27536	NNS	denotes	phenotypes
T5059	27536-27537	.	denotes	.
T5060	27537-27754	sentence	denotes	We conclude that the defects leading to embryonic lethality and aberrant terminal differentiation of the skin, hair, and blood represent two qualitatively and/or quantitatively different transcriptional deficiencies.
T5061	27538-27540	PRP	denotes	We
T5062	27541-27549	VBP	denotes	conclude
T5063	27550-27554	IN	denotes	that
T5065	27555-27558	DT	denotes	the
T5066	27559-27566	NNS	denotes	defects
T5067	27567-27574	VBG	denotes	leading
T5068	27575-27577	IN	denotes	to
T5069	27578-27587	JJ	denotes	embryonic
T5070	27588-27597	NN	denotes	lethality
T5071	27598-27601	CC	denotes	and
T5072	27602-27610	JJ	denotes	aberrant
T5074	27611-27619	JJ	denotes	terminal
T5073	27620-27635	NN	denotes	differentiation
T5075	27636-27638	IN	denotes	of
T5076	27639-27642	DT	denotes	the
T5077	27643-27647	NN	denotes	skin
T5078	27647-27649	,	denotes	,
T5079	27649-27653	NN	denotes	hair
T5080	27653-27655	,	denotes	,
T5081	27655-27658	CC	denotes	and
T5082	27659-27664	NN	denotes	blood
T5064	27665-27674	VBP	denotes	represent
T5083	27675-27678	CD	denotes	two
T5085	27679-27692	RB	denotes	qualitatively
T5087	27693-27696	CC	denotes	and
T5088	27696-27697	HYPH	denotes	/
T5089	27697-27699	CC	denotes	or
T5090	27700-27714	RB	denotes	quantitatively
T5086	27715-27724	JJ	denotes	different
T5091	27725-27740	JJ	denotes	transcriptional
T5084	27741-27753	NNS	denotes	deficiencies
T5092	27753-27754	.	denotes	.
T5093	27754-27945	sentence	denotes	During early embryonic development, XpdTTD is dominant over the Xpd†XPCS and Xpd†XP alleles, whereas later in the ontogenesis of skin, hair-shaft, and blood cells, the situation is reversed.
T5094	27755-27761	IN	denotes	During
T5096	27762-27767	JJ	denotes	early
T5098	27768-27777	JJ	denotes	embryonic
T5097	27778-27789	NN	denotes	development
T5099	27789-27791	,	denotes	,
T5100	27791-27797	NN	denotes	XpdTTD
T5095	27798-27800	VBZ	denotes	is
T5101	27801-27809	JJ	denotes	dominant
T5102	27810-27814	IN	denotes	over
T5103	27815-27818	DT	denotes	the
T5105	27819-27827	NN	denotes	Xpd†XPCS
T5106	27828-27831	CC	denotes	and
T5107	27832-27838	NN	denotes	Xpd†XP
T5104	27839-27846	NNS	denotes	alleles
T5108	27846-27848	,	denotes	,
T5109	27848-27855	IN	denotes	whereas
T5111	27856-27861	RB	denotes	later
T5112	27862-27864	IN	denotes	in
T5113	27865-27868	DT	denotes	the
T5114	27869-27880	NN	denotes	ontogenesis
T5115	27881-27883	IN	denotes	of
T5116	27884-27888	NN	denotes	skin
T5117	27888-27890	,	denotes	,
T5118	27890-27894	NN	denotes	hair
T5120	27894-27895	HYPH	denotes	-
T5119	27895-27900	NN	denotes	shaft
T5121	27900-27902	,	denotes	,
T5122	27902-27905	CC	denotes	and
T5123	27906-27911	NN	denotes	blood
T5124	27912-27917	NNS	denotes	cells
T5125	27917-27919	,	denotes	,
T5126	27919-27922	DT	denotes	the
T5127	27923-27932	NN	denotes	situation
T5128	27933-27935	VBZ	denotes	is
T5110	27936-27944	VBN	denotes	reversed
T5129	27944-27945	.	denotes	.
T5130	27945-28188	sentence	denotes	In its role in the repair of UV photolesions, the Xpd†XPCS allele imparted a clear UV survival benefit over a single XpdTTD allele or two XpdXPCS alleles independent of expression levels, which is consistent with interallelic complementation.
T5131	27946-27948	IN	denotes	In
T5133	27949-27952	PRP$	denotes	its
T5134	27953-27957	NN	denotes	role
T5135	27958-27960	IN	denotes	in
T5136	27961-27964	DT	denotes	the
T5137	27965-27971	NN	denotes	repair
T5138	27972-27974	IN	denotes	of
T5139	27975-27977	NN	denotes	UV
T5140	27978-27990	NNS	denotes	photolesions
T5141	27990-27992	,	denotes	,
T5142	27992-27995	DT	denotes	the
T5144	27996-28004	NN	denotes	Xpd†XPCS
T5143	28005-28011	NN	denotes	allele
T5132	28012-28020	VBD	denotes	imparted
T5145	28021-28022	DT	denotes	a
T5147	28023-28028	JJ	denotes	clear
T5148	28029-28031	NN	denotes	UV
T5149	28032-28040	NN	denotes	survival
T5146	28041-28048	NN	denotes	benefit
T5150	28049-28053	IN	denotes	over
T5151	28054-28055	DT	denotes	a
T5153	28056-28062	JJ	denotes	single
T5154	28063-28069	NN	denotes	XpdTTD
T5152	28070-28076	NN	denotes	allele
T5155	28077-28079	CC	denotes	or
T5156	28080-28083	CD	denotes	two
T5158	28084-28091	NN	denotes	XpdXPCS
T5157	28092-28099	NNS	denotes	alleles
T5159	28100-28111	JJ	denotes	independent
T5160	28112-28114	IN	denotes	of
T5161	28115-28125	NN	denotes	expression
T5162	28126-28132	NNS	denotes	levels
T5163	28132-28134	,	denotes	,
T5164	28134-28139	WDT	denotes	which
T5165	28140-28142	VBZ	denotes	is
T5166	28143-28153	JJ	denotes	consistent
T5167	28154-28158	IN	denotes	with
T5168	28159-28171	JJ	denotes	interallelic
T5169	28172-28187	NN	denotes	complementation
T5170	28187-28188	.	denotes	.
T5171	28188-28408	sentence	denotes	However, the observation that no other cellular or biochemical UV-related parameters were improved in XpdTTD/ †XPCS argues against complementation of this repair activity in the rescue of TTD progeroid symptoms in vivo.
T5172	28189-28196	RB	denotes	However
T5174	28196-28198	,	denotes	,
T5175	28198-28201	DT	denotes	the
T5176	28202-28213	NN	denotes	observation
T5177	28214-28218	IN	denotes	that
T5179	28219-28221	DT	denotes	no
T5181	28222-28227	JJ	denotes	other
T5182	28228-28236	JJ	denotes	cellular
T5183	28237-28239	CC	denotes	or
T5184	28240-28251	JJ	denotes	biochemical
T5185	28252-28254	NN	denotes	UV
T5187	28254-28255	HYPH	denotes	-
T5186	28255-28262	VBN	denotes	related
T5180	28263-28273	NNS	denotes	parameters
T5188	28274-28278	VBD	denotes	were
T5178	28279-28287	VBN	denotes	improved
T5189	28288-28290	IN	denotes	in
T5190	28291-28297	NN	denotes	XpdTTD
T5192	28297-28298	HYPH	denotes	/
T5191	28298-28304	NN	denotes	†XPCS
T5173	28305-28311	VBZ	denotes	argues
T5193	28312-28319	IN	denotes	against
T5194	28320-28335	NN	denotes	complementation
T5195	28336-28338	IN	denotes	of
T5196	28339-28343	DT	denotes	this
T5198	28344-28350	NN	denotes	repair
T5197	28351-28359	NN	denotes	activity
T5199	28360-28362	IN	denotes	in
T5200	28363-28366	DT	denotes	the
T5201	28367-28373	NN	denotes	rescue
T5202	28374-28376	IN	denotes	of
T5203	28377-28380	NN	denotes	TTD
T5205	28381-28390	JJ	denotes	progeroid
T5204	28391-28399	NNS	denotes	symptoms
T5206	28400-28402	FW	denotes	in
T5207	28403-28407	FW	denotes	vivo
T5208	28407-28408	.	denotes	.
T5295	28410-28422	JJ	denotes	Interallelic
T5296	28423-28438	NN	denotes	Complementation
T5297	28439-28442	CC	denotes	and
T5298	28443-28446	NN	denotes	XPD
T5299	28447-28455	NN	denotes	Function
T5300	28455-28539	sentence	denotes	What does interallelic complementation tell us about the mechanism of XPD function?
T5301	28456-28460	WP	denotes	What
T5303	28461-28465	VBZ	denotes	does
T5304	28466-28478	JJ	denotes	interallelic
T5305	28479-28494	NN	denotes	complementation
T5302	28495-28499	VB	denotes	tell
T5306	28500-28502	PRP	denotes	us
T5307	28503-28508	IN	denotes	about
T5308	28509-28512	DT	denotes	the
T5309	28513-28522	NN	denotes	mechanism
T5310	28523-28525	IN	denotes	of
T5311	28526-28529	NN	denotes	XPD
T5312	28530-28538	NN	denotes	function
T5313	28538-28539	.	denotes	?
T5314	28539-28648	sentence	denotes	Interallelic complementation is most often observed in multimeric proteins with multiple functional domains.
T5315	28540-28552	JJ	denotes	Interallelic
T5316	28553-28568	NN	denotes	complementation
T5318	28569-28571	VBZ	denotes	is
T5319	28572-28576	RBS	denotes	most
T5320	28577-28582	RB	denotes	often
T5317	28583-28591	VBN	denotes	observed
T5321	28592-28594	IN	denotes	in
T5322	28595-28605	JJ	denotes	multimeric
T5323	28606-28614	NN	denotes	proteins
T5324	28615-28619	IN	denotes	with
T5325	28620-28628	JJ	denotes	multiple
T5327	28629-28639	JJ	denotes	functional
T5326	28640-28647	NNS	denotes	domains
T5328	28647-28648	.	denotes	.
T5329	28648-28867	sentence	denotes	Unfortunately, the structure–function relationship between disease-causing mutations and XPD functional domains, including detailed structural information on XPD or even its stoichiometry within TFIIH, remains unknown.
T5330	28649-28662	RB	denotes	Unfortunately
T5332	28662-28664	,	denotes	,
T5333	28664-28667	DT	denotes	the
T5335	28668-28677	NN	denotes	structure
T5337	28677-28678	HYPH	denotes	–
T5336	28678-28686	NN	denotes	function
T5334	28687-28699	NN	denotes	relationship
T5338	28700-28707	IN	denotes	between
T5339	28708-28715	NN	denotes	disease
T5341	28715-28716	HYPH	denotes	-
T5340	28716-28723	VBG	denotes	causing
T5342	28724-28733	NNS	denotes	mutations
T5343	28734-28737	CC	denotes	and
T5344	28738-28741	NN	denotes	XPD
T5346	28742-28752	JJ	denotes	functional
T5345	28753-28760	NNS	denotes	domains
T5347	28760-28762	,	denotes	,
T5348	28762-28771	VBG	denotes	including
T5349	28772-28780	JJ	denotes	detailed
T5351	28781-28791	JJ	denotes	structural
T5350	28792-28803	NN	denotes	information
T5352	28804-28806	IN	denotes	on
T5353	28807-28810	NN	denotes	XPD
T5354	28811-28813	CC	denotes	or
T5355	28814-28818	RB	denotes	even
T5357	28819-28822	PRP$	denotes	its
T5356	28823-28836	NN	denotes	stoichiometry
T5358	28837-28843	IN	denotes	within
T5359	28844-28849	NN	denotes	TFIIH
T5360	28849-28851	,	denotes	,
T5331	28851-28858	VBZ	denotes	remains
T5361	28859-28866	JJ	denotes	unknown
T5362	28866-28867	.	denotes	.
T5363	28867-29136	sentence	denotes	However, based on the ability of cell extracts that are defective in two different TFIIH components (XPD and XPB) to complement NER activity in vitro [26], it is likely that TFIIH (or its components) can either multimerise or exchange at least during the NER reaction.
T5364	28868-28875	RB	denotes	However
T5366	28875-28877	,	denotes	,
T5367	28877-28882	VBN	denotes	based
T5368	28883-28885	IN	denotes	on
T5369	28886-28889	DT	denotes	the
T5370	28890-28897	NN	denotes	ability
T5371	28898-28900	IN	denotes	of
T5372	28901-28905	NN	denotes	cell
T5373	28906-28914	NNS	denotes	extracts
T5374	28915-28919	WDT	denotes	that
T5375	28920-28923	VBP	denotes	are
T5376	28924-28933	JJ	denotes	defective
T5377	28934-28936	IN	denotes	in
T5378	28937-28940	CD	denotes	two
T5380	28941-28950	JJ	denotes	different
T5381	28951-28956	NN	denotes	TFIIH
T5379	28957-28967	NNS	denotes	components
T5382	28968-28969	-LRB-	denotes	(
T5383	28969-28972	NN	denotes	XPD
T5384	28973-28976	CC	denotes	and
T5385	28977-28980	NN	denotes	XPB
T5386	28980-28981	-RRB-	denotes	)
T5387	28982-28984	TO	denotes	to
T5388	28985-28995	VB	denotes	complement
T5389	28996-28999	NN	denotes	NER
T5390	29000-29008	NN	denotes	activity
T5391	29009-29011	FW	denotes	in
T5392	29012-29017	FW	denotes	vitro
T5393	29018-29019	-LRB-	denotes	[
T5394	29019-29021	CD	denotes	26
T5395	29021-29022	-RRB-	denotes	]
T5396	29022-29024	,	denotes	,
T5397	29024-29026	PRP	denotes	it
T5365	29027-29029	VBZ	denotes	is
T5398	29030-29036	JJ	denotes	likely
T5399	29037-29041	IN	denotes	that
T5401	29042-29047	NN	denotes	TFIIH
T5402	29048-29049	-LRB-	denotes	(
T5403	29049-29051	CC	denotes	or
T5404	29052-29055	PRP$	denotes	its
T5405	29056-29066	NNS	denotes	components
T5406	29066-29067	-RRB-	denotes	)
T5407	29068-29071	MD	denotes	can
T5408	29072-29078	CC	denotes	either
T5400	29079-29090	VB	denotes	multimerise
T5409	29091-29093	CC	denotes	or
T5410	29094-29102	VB	denotes	exchange
T5411	29103-29105	RB	denotes	at
T5412	29106-29111	RBS	denotes	least
T5413	29112-29118	IN	denotes	during
T5414	29119-29122	DT	denotes	the
T5416	29123-29126	NN	denotes	NER
T5415	29127-29135	NN	denotes	reaction
T5417	29135-29136	.	denotes	.
T5418	29136-29209	sentence	denotes	Furthermore, XPD is known to be a “loosely bound” subunit of TFIIH [27].
T5419	29137-29148	RB	denotes	Furthermore
T5421	29148-29150	,	denotes	,
T5422	29150-29153	NN	denotes	XPD
T5423	29154-29156	VBZ	denotes	is
T5420	29157-29162	VBN	denotes	known
T5424	29163-29165	TO	denotes	to
T5425	29166-29168	VB	denotes	be
T5426	29169-29170	DT	denotes	a
T5428	29171-29172	RB	denotes	“
T5429	29172-29179	RB	denotes	loosely
T5430	29180-29185	VBN	denotes	bound
T5431	29185-29186	''	denotes	”
T5427	29187-29194	NN	denotes	subunit
T5432	29195-29197	IN	denotes	of
T5433	29198-29203	NN	denotes	TFIIH
T5434	29204-29205	-LRB-	denotes	[
T5435	29205-29207	CD	denotes	27
T5436	29207-29208	-RRB-	denotes	]
T5437	29208-29209	.	denotes	.
T5438	29209-29566	sentence	denotes	We thus envisage the molecular mechanism of interallelic complementation to involve the exchange of XPD molecules within the TFIIH complex or turnover of TFIIH complexes containing different XPD molecules at the site of DNA damage during the course of the global genome as well as transcription-coupled repair of either UV-induced or endogenous DNA damage.
T5439	29210-29212	PRP	denotes	We
T5441	29213-29217	RB	denotes	thus
T5440	29218-29226	VBP	denotes	envisage
T5442	29227-29230	DT	denotes	the
T5444	29231-29240	JJ	denotes	molecular
T5443	29241-29250	NN	denotes	mechanism
T5446	29251-29253	IN	denotes	of
T5447	29254-29266	JJ	denotes	interallelic
T5448	29267-29282	NN	denotes	complementation
T5449	29283-29285	TO	denotes	to
T5445	29286-29293	VB	denotes	involve
T5450	29294-29297	DT	denotes	the
T5451	29298-29306	NN	denotes	exchange
T5452	29307-29309	IN	denotes	of
T5453	29310-29313	NN	denotes	XPD
T5454	29314-29323	NNS	denotes	molecules
T5455	29324-29330	IN	denotes	within
T5456	29331-29334	DT	denotes	the
T5458	29335-29340	NN	denotes	TFIIH
T5457	29341-29348	NN	denotes	complex
T5459	29349-29351	CC	denotes	or
T5460	29352-29360	NN	denotes	turnover
T5461	29361-29363	IN	denotes	of
T5462	29364-29369	NN	denotes	TFIIH
T5463	29370-29379	NNS	denotes	complexes
T5464	29380-29390	VBG	denotes	containing
T5465	29391-29400	JJ	denotes	different
T5467	29401-29404	NN	denotes	XPD
T5466	29405-29414	NNS	denotes	molecules
T5468	29415-29417	IN	denotes	at
T5469	29418-29421	DT	denotes	the
T5470	29422-29426	NN	denotes	site
T5471	29427-29429	IN	denotes	of
T5472	29430-29433	NN	denotes	DNA
T5473	29434-29440	NN	denotes	damage
T5474	29441-29447	IN	denotes	during
T5475	29448-29451	DT	denotes	the
T5476	29452-29458	NN	denotes	course
T5477	29459-29461	IN	denotes	of
T5478	29462-29465	DT	denotes	the
T5480	29466-29472	JJ	denotes	global
T5479	29473-29479	NN	denotes	genome
T5481	29480-29482	RB	denotes	as
T5483	29483-29487	RB	denotes	well
T5482	29488-29490	IN	denotes	as
T5484	29491-29504	NN	denotes	transcription
T5486	29504-29505	HYPH	denotes	-
T5485	29505-29512	VBN	denotes	coupled
T5487	29513-29519	NN	denotes	repair
T5488	29520-29522	IN	denotes	of
T5489	29523-29529	CC	denotes	either
T5491	29530-29532	NN	denotes	UV
T5493	29532-29533	HYPH	denotes	-
T5492	29533-29540	VBN	denotes	induced
T5494	29541-29543	CC	denotes	or
T5495	29544-29554	JJ	denotes	endogenous
T5496	29555-29558	NN	denotes	DNA
T5490	29559-29565	NN	denotes	damage
T5497	29565-29566	.	denotes	.
T5607	29568-29569	DT	denotes	A
T5609	29570-29579	JJ	denotes	Biallelic
T5608	29580-29588	NN	denotes	Paradigm
T5610	29589-29592	IN	denotes	for
T5611	29593-29596	NN	denotes	XPD
T5612	29597-29606	NNS	denotes	Disorders
T5613	29606-29888	sentence	denotes	Recently, proteins originating from presumed null alleles were biochemically characterised as inactive in basal transcription [27], providing an explanation as to why these alleles failed to rescue lethality in haploid S. pombe with a null mutation in the XPD homologue rad15 [19].
T5614	29607-29615	RB	denotes	Recently
T5616	29615-29617	,	denotes	,
T5617	29617-29625	NN	denotes	proteins
T5618	29626-29637	VBG	denotes	originating
T5619	29638-29642	IN	denotes	from
T5620	29643-29651	VBN	denotes	presumed
T5622	29652-29656	JJ	denotes	null
T5621	29657-29664	NNS	denotes	alleles
T5623	29665-29669	VBD	denotes	were
T5624	29670-29683	RB	denotes	biochemically
T5615	29684-29697	VBN	denotes	characterised
T5625	29698-29700	IN	denotes	as
T5626	29701-29709	JJ	denotes	inactive
T5627	29710-29712	IN	denotes	in
T5628	29713-29718	JJ	denotes	basal
T5629	29719-29732	NN	denotes	transcription
T5630	29733-29734	-LRB-	denotes	[
T5631	29734-29736	CD	denotes	27
T5632	29736-29737	-RRB-	denotes	]
T5633	29737-29739	,	denotes	,
T5634	29739-29748	VBG	denotes	providing
T5635	29749-29751	DT	denotes	an
T5636	29752-29763	NN	denotes	explanation
T5637	29764-29766	IN	denotes	as
T5638	29767-29769	IN	denotes	to
T5639	29770-29773	WRB	denotes	why
T5641	29774-29779	DT	denotes	these
T5642	29780-29787	NNS	denotes	alleles
T5640	29788-29794	VBD	denotes	failed
T5643	29795-29797	TO	denotes	to
T5644	29798-29804	VB	denotes	rescue
T5645	29805-29814	NN	denotes	lethality
T5646	29815-29817	IN	denotes	in
T5647	29818-29825	JJ	denotes	haploid
T5649	29826-29828	FW	denotes	S.
T5648	29829-29834	FW	denotes	pombe
T5650	29835-29839	IN	denotes	with
T5651	29840-29841	DT	denotes	a
T5653	29842-29846	JJ	denotes	null
T5652	29847-29855	NN	denotes	mutation
T5654	29856-29858	IN	denotes	in
T5655	29859-29862	DT	denotes	the
T5657	29863-29866	NN	denotes	XPD
T5656	29867-29876	NN	denotes	homologue
T5658	29877-29882	NN	denotes	rad15
T5659	29883-29884	-LRB-	denotes	[
T5660	29884-29886	CD	denotes	19
T5661	29886-29887	-RRB-	denotes	]
T5662	29887-29888	.	denotes	.
T5663	29888-30120	sentence	denotes	Our data suggest that certain presumed null alleles, although unable on their own to support basal transcription, may in fact have a substantial impact on disease outcome in compound heterozygous humans, as they do in mouse models.
T5664	29889-29892	PRP$	denotes	Our
T5665	29893-29897	NNS	denotes	data
T5666	29898-29905	VBP	denotes	suggest
T5667	29906-29910	IN	denotes	that
T5669	29911-29918	JJ	denotes	certain
T5671	29919-29927	VBN	denotes	presumed
T5672	29928-29932	JJ	denotes	null
T5670	29933-29940	NNS	denotes	alleles
T5673	29940-29942	,	denotes	,
T5674	29942-29950	IN	denotes	although
T5675	29951-29957	JJ	denotes	unable
T5676	29958-29960	IN	denotes	on
T5678	29961-29966	PRP$	denotes	their
T5679	29967-29970	NN	denotes	own
T5680	29971-29973	TO	denotes	to
T5677	29974-29981	VB	denotes	support
T5681	29982-29987	JJ	denotes	basal
T5682	29988-30001	NN	denotes	transcription
T5683	30001-30003	,	denotes	,
T5684	30003-30006	MD	denotes	may
T5685	30007-30009	IN	denotes	in
T5686	30010-30014	NN	denotes	fact
T5668	30015-30019	VB	denotes	have
T5687	30020-30021	DT	denotes	a
T5689	30022-30033	JJ	denotes	substantial
T5688	30034-30040	NN	denotes	impact
T5690	30041-30043	IN	denotes	on
T5691	30044-30051	NN	denotes	disease
T5692	30052-30059	NN	denotes	outcome
T5693	30060-30062	IN	denotes	in
T5694	30063-30071	NN	denotes	compound
T5696	30072-30084	JJ	denotes	heterozygous
T5695	30085-30091	NNS	denotes	humans
T5697	30091-30093	,	denotes	,
T5698	30093-30095	IN	denotes	as
T5700	30096-30100	PRP	denotes	they
T5701	30101-30103	VBP	denotes	do
T5699	30104-30106	IN	denotes	in
T5702	30107-30112	NN	denotes	mouse
T5703	30113-30119	NNS	denotes	models
T5704	30119-30120	.	denotes	.
T5705	30120-30329	sentence	denotes	Clinical evidence in support of this hypothesis comes from a number of XP complementation group D patients that do not fit within the framework of the current monoallelic paradigm of XPD disorders (Figure 5).
T5706	30121-30129	JJ	denotes	Clinical
T5707	30130-30138	NN	denotes	evidence
T5709	30139-30141	IN	denotes	in
T5710	30142-30149	NN	denotes	support
T5711	30150-30152	IN	denotes	of
T5712	30153-30157	DT	denotes	this
T5713	30158-30168	NN	denotes	hypothesis
T5708	30169-30174	VBZ	denotes	comes
T5714	30175-30179	IN	denotes	from
T5715	30180-30181	DT	denotes	a
T5716	30182-30188	NN	denotes	number
T5717	30189-30191	IN	denotes	of
T5718	30192-30194	NN	denotes	XP
T5720	30195-30210	NN	denotes	complementation
T5721	30211-30216	NN	denotes	group
T5722	30217-30218	NN	denotes	D
T5719	30219-30227	NNS	denotes	patients
T5723	30228-30232	WDT	denotes	that
T5725	30233-30235	VBP	denotes	do
T5726	30236-30239	RB	denotes	not
T5724	30240-30243	VB	denotes	fit
T5727	30244-30250	IN	denotes	within
T5728	30251-30254	DT	denotes	the
T5729	30255-30264	NN	denotes	framework
T5730	30265-30267	IN	denotes	of
T5731	30268-30271	DT	denotes	the
T5733	30272-30279	JJ	denotes	current
T5734	30280-30291	JJ	denotes	monoallelic
T5732	30292-30300	NN	denotes	paradigm
T5735	30301-30303	IN	denotes	of
T5736	30304-30307	NN	denotes	XPD
T5737	30308-30317	NNS	denotes	disorders
T5738	30318-30319	-LRB-	denotes	(
T5739	30319-30325	NN	denotes	Figure
T5740	30326-30327	CD	denotes	5
T5741	30327-30328	-RRB-	denotes	)
T5742	30328-30329	.	denotes	.
T5743	30329-30757	sentence	denotes	In contrast to two hemizygous XPDXPCS patients carrying the XPDG47R- or XPDR666W-encoding alleles who died of the disease before 2 y of age, two compound heterozygous XPDXPCS patients carrying the same XPDG47R- or XPDR666W-encoding alleles in addition to the presumed null XPDL461V+del716−730 both had considerably milder disease symptoms and survived more than ten times longer (A. Lehmann, personal communication) (Figure 5).
T5744	30330-30332	IN	denotes	In
T5746	30333-30341	NN	denotes	contrast
T5747	30342-30344	IN	denotes	to
T5748	30345-30348	CD	denotes	two
T5750	30349-30359	JJ	denotes	hemizygous
T5751	30360-30367	NN	denotes	XPDXPCS
T5749	30368-30376	NNS	denotes	patients
T5752	30377-30385	VBG	denotes	carrying
T5753	30386-30389	DT	denotes	the
T5755	30390-30397	NN	denotes	XPDG47R
T5757	30397-30398	HYPH	denotes	-
T5758	30399-30401	CC	denotes	or
T5759	30402-30410	NN	denotes	XPDR666W
T5760	30410-30411	HYPH	denotes	-
T5756	30411-30419	VBG	denotes	encoding
T5754	30420-30427	NNS	denotes	alleles
T5761	30428-30431	WP	denotes	who
T5762	30432-30436	VBD	denotes	died
T5763	30437-30439	IN	denotes	of
T5764	30440-30443	DT	denotes	the
T5765	30444-30451	NN	denotes	disease
T5766	30452-30458	IN	denotes	before
T5767	30459-30460	CD	denotes	2
T5768	30461-30462	NNS	denotes	y
T5769	30463-30465	IN	denotes	of
T5770	30466-30469	NN	denotes	age
T5771	30469-30471	,	denotes	,
T5772	30471-30474	CD	denotes	two
T5774	30475-30483	JJ	denotes	compound
T5775	30484-30496	JJ	denotes	heterozygous
T5776	30497-30504	NN	denotes	XPDXPCS
T5773	30505-30513	NNS	denotes	patients
T5777	30514-30522	VBG	denotes	carrying
T5778	30523-30526	DT	denotes	the
T5780	30527-30531	JJ	denotes	same
T5781	30532-30539	NN	denotes	XPDG47R
T5783	30539-30540	HYPH	denotes	-
T5784	30541-30543	CC	denotes	or
T5785	30544-30552	NN	denotes	XPDR666W
T5786	30552-30553	HYPH	denotes	-
T5782	30553-30561	VBG	denotes	encoding
T5779	30562-30569	NNS	denotes	alleles
T5787	30570-30572	IN	denotes	in
T5788	30573-30581	NN	denotes	addition
T5789	30582-30584	IN	denotes	to
T5790	30585-30588	DT	denotes	the
T5792	30589-30597	VBN	denotes	presumed
T5793	30598-30602	JJ	denotes	null
T5794	30603-30611	NN	denotes	XPDL461V
T5795	30611-30612	SYM	denotes	+
T5796	30612-30618	NN	denotes	del716
T5797	30618-30619	HYPH	denotes	−
T5791	30619-30622	NN	denotes	730
T5798	30623-30627	DT	denotes	both
T5745	30628-30631	VBD	denotes	had
T5799	30632-30644	RB	denotes	considerably
T5800	30645-30651	JJR	denotes	milder
T5802	30652-30659	NN	denotes	disease
T5801	30660-30668	NNS	denotes	symptoms
T5803	30669-30672	CC	denotes	and
T5804	30673-30681	VBD	denotes	survived
T5805	30682-30686	JJR	denotes	more
T5807	30687-30691	IN	denotes	than
T5806	30692-30695	CD	denotes	ten
T5808	30696-30701	NNS	denotes	times
T5809	30702-30708	RBR	denotes	longer
T5810	30709-30710	-LRB-	denotes	(
T5811	30710-30712	NNP	denotes	A.
T5812	30713-30720	NNP	denotes	Lehmann
T5813	30720-30722	,	denotes	,
T5814	30722-30730	JJ	denotes	personal
T5815	30731-30744	NN	denotes	communication
T5816	30744-30745	-RRB-	denotes	)
T5817	30746-30747	-LRB-	denotes	(
T5818	30747-30753	NN	denotes	Figure
T5819	30754-30755	CD	denotes	5
T5820	30755-30756	-RRB-	denotes	)
T5821	30756-30757	.	denotes	.
T5822	30757-30872	sentence	denotes	Compound heterozygosity is also associated with the recently reported combination XP and TTD (XPTTD) syndrome [8].
T5823	30758-30766	NN	denotes	Compound
T5824	30767-30781	NN	denotes	heterozygosity
T5826	30782-30784	VBZ	denotes	is
T5827	30785-30789	RB	denotes	also
T5825	30790-30800	VBN	denotes	associated
T5828	30801-30805	IN	denotes	with
T5829	30806-30809	DT	denotes	the
T5831	30810-30818	RB	denotes	recently
T5832	30819-30827	VBN	denotes	reported
T5833	30828-30839	NN	denotes	combination
T5834	30840-30842	NN	denotes	XP
T5835	30843-30846	CC	denotes	and
T5836	30847-30850	NN	denotes	TTD
T5837	30851-30852	-LRB-	denotes	(
T5838	30852-30857	NN	denotes	XPTTD
T5839	30857-30858	-RRB-	denotes	)
T5830	30859-30867	NN	denotes	syndrome
T5840	30868-30869	-LRB-	denotes	[
T5841	30869-30870	CD	denotes	8
T5842	30870-30871	-RRB-	denotes	]
T5843	30871-30872	.	denotes	.
T5844	30872-31017	sentence	denotes	Similar to the XpdTTD/†XPCS and XpdTTD/†XP mice described here, both patients with XPTTD described so far had intermediate hair cysteine values.
T5845	30873-30880	JJ	denotes	Similar
T5847	30881-30883	IN	denotes	to
T5848	30884-30887	DT	denotes	the
T5850	30888-30894	NN	denotes	XpdTTD
T5852	30894-30895	HYPH	denotes	/
T5851	30895-30900	NN	denotes	†XPCS
T5853	30901-30904	CC	denotes	and
T5854	30905-30911	NN	denotes	XpdTTD
T5856	30911-30912	HYPH	denotes	/
T5855	30912-30915	NN	denotes	†XP
T5849	30916-30920	NNS	denotes	mice
T5857	30921-30930	VBN	denotes	described
T5858	30931-30935	RB	denotes	here
T5859	30935-30937	,	denotes	,
T5860	30937-30941	DT	denotes	both
T5861	30942-30950	NNS	denotes	patients
T5862	30951-30955	IN	denotes	with
T5863	30956-30961	NN	denotes	XPTTD
T5864	30962-30971	VBN	denotes	described
T5865	30972-30974	RB	denotes	so
T5866	30975-30978	RB	denotes	far
T5846	30979-30982	VBD	denotes	had
T5867	30983-30995	JJ	denotes	intermediate
T5869	30996-31000	NN	denotes	hair
T5870	31001-31009	NN	denotes	cysteine
T5868	31010-31016	NNS	denotes	values
T5871	31016-31017	.	denotes	.
T5872	31017-31159	sentence	denotes	Furthermore, XPTTD patient XP38BR carried a “causative” TTD mutation in one allele and a novel point mutation encoding XPDL485P in the other.
T5873	31018-31029	RB	denotes	Furthermore
T5875	31029-31031	,	denotes	,
T5876	31031-31036	NN	denotes	XPTTD
T5878	31037-31044	NN	denotes	patient
T5877	31045-31051	NN	denotes	XP38BR
T5874	31052-31059	VBD	denotes	carried
T5879	31060-31061	DT	denotes	a
T5881	31062-31063	``	denotes	“
T5882	31063-31072	JJ	denotes	causative
T5883	31072-31073	''	denotes	”
T5884	31074-31077	NN	denotes	TTD
T5880	31078-31086	NN	denotes	mutation
T5885	31087-31089	IN	denotes	in
T5886	31090-31093	CD	denotes	one
T5887	31094-31100	NN	denotes	allele
T5888	31101-31104	CC	denotes	and
T5889	31105-31106	DT	denotes	a
T5891	31107-31112	JJ	denotes	novel
T5892	31113-31118	NN	denotes	point
T5890	31119-31127	NN	denotes	mutation
T5893	31128-31136	VBG	denotes	encoding
T5894	31137-31145	NN	denotes	XPDL485P
T5895	31146-31148	IN	denotes	in
T5896	31149-31152	DT	denotes	the
T5897	31153-31158	JJ	denotes	other
T5898	31158-31159	.	denotes	.
T5899	31159-31447	sentence	denotes	Although the XPDL485P-encoding allele fails to complement viability in the haploid S. pombe rad15 deletion strain and is thus interpretable as a null allele [8], we nonetheless suggest that the combined XPTTD phenotype in this patient involves phenotypic contributions from both alleles.
T5900	31160-31168	IN	denotes	Although
T5902	31169-31172	DT	denotes	the
T5904	31173-31181	NN	denotes	XPDL485P
T5906	31181-31182	HYPH	denotes	-
T5905	31182-31190	VBG	denotes	encoding
T5903	31191-31197	NN	denotes	allele
T5901	31198-31203	VBZ	denotes	fails
T5908	31204-31206	TO	denotes	to
T5909	31207-31217	VB	denotes	complement
T5910	31218-31227	NN	denotes	viability
T5911	31228-31230	IN	denotes	in
T5912	31231-31234	DT	denotes	the
T5914	31235-31242	JJ	denotes	haploid
T5915	31243-31245	FW	denotes	S.
T5916	31246-31251	FW	denotes	pombe
T5917	31252-31257	NN	denotes	rad15
T5918	31258-31266	NN	denotes	deletion
T5913	31267-31273	NN	denotes	strain
T5919	31274-31277	CC	denotes	and
T5920	31278-31280	VBZ	denotes	is
T5921	31281-31285	RB	denotes	thus
T5922	31286-31299	JJ	denotes	interpretable
T5923	31300-31302	IN	denotes	as
T5924	31303-31304	DT	denotes	a
T5926	31305-31309	JJ	denotes	null
T5925	31310-31316	NN	denotes	allele
T5927	31317-31318	-LRB-	denotes	[
T5928	31318-31319	CD	denotes	8
T5929	31319-31320	-RRB-	denotes	]
T5930	31320-31322	,	denotes	,
T5931	31322-31324	PRP	denotes	we
T5932	31325-31336	RB	denotes	nonetheless
T5907	31337-31344	VBP	denotes	suggest
T5933	31345-31349	IN	denotes	that
T5935	31350-31353	DT	denotes	the
T5937	31354-31362	JJ	denotes	combined
T5938	31363-31368	NN	denotes	XPTTD
T5936	31369-31378	NN	denotes	phenotype
T5939	31379-31381	IN	denotes	in
T5940	31382-31386	DT	denotes	this
T5941	31387-31394	NN	denotes	patient
T5934	31395-31403	VBZ	denotes	involves
T5942	31404-31414	JJ	denotes	phenotypic
T5943	31415-31428	NNS	denotes	contributions
T5944	31429-31433	IN	denotes	from
T5945	31434-31438	DT	denotes	both
T5946	31439-31446	NNS	denotes	alleles
T5947	31446-31447	.	denotes	.
T5948	31447-31580	sentence	denotes	Taken together, these data suggest a shift to a biallelic paradigm for compound heterozygous patients in XP complementation group D.
T5949	31448-31453	VBN	denotes	Taken
T5951	31454-31462	RB	denotes	together
T5952	31462-31464	,	denotes	,
T5953	31464-31469	DT	denotes	these
T5954	31470-31474	NNS	denotes	data
T5950	31475-31482	VBP	denotes	suggest
T5955	31483-31484	DT	denotes	a
T5956	31485-31490	NN	denotes	shift
T5957	31491-31493	IN	denotes	to
T5958	31494-31495	DT	denotes	a
T5960	31496-31505	JJ	denotes	biallelic
T5959	31506-31514	NN	denotes	paradigm
T5961	31515-31518	IN	denotes	for
T5962	31519-31527	NN	denotes	compound
T5964	31528-31540	JJ	denotes	heterozygous
T5963	31541-31549	NNS	denotes	patients
T5965	31550-31552	IN	denotes	in
T5966	31553-31555	NN	denotes	XP
T5968	31556-31571	NN	denotes	complementation
T5969	31572-31577	NN	denotes	group
T5967	31578-31579	NN	denotes	D
T5970	31579-31580	.	denotes	.
T9280	31591-31599	NN	denotes	Genotype
T9282	31599-31600	HYPH	denotes	–
T9281	31600-31609	NN	denotes	Phenotype
T9283	31610-31623	NNS	denotes	Relationships
T9284	31624-31626	IN	denotes	in
T9285	31627-31630	NN	denotes	XPD
T9286	31631-31640	NNS	denotes	Disorders
T9287	31640-31753	sentence	denotes	According to the current monoallelic hypothesis, phenotype is determined solely by the causative allele product.
T9288	31641-31650	VBG	denotes	According
T9290	31651-31653	IN	denotes	to
T9291	31654-31657	DT	denotes	the
T9293	31658-31665	JJ	denotes	current
T9294	31666-31677	JJ	denotes	monoallelic
T9292	31678-31688	NN	denotes	hypothesis
T9295	31688-31690	,	denotes	,
T9296	31690-31699	NN	denotes	phenotype
T9297	31700-31702	VBZ	denotes	is
T9289	31703-31713	VBN	denotes	determined
T9298	31714-31720	RB	denotes	solely
T9299	31721-31723	IN	denotes	by
T9300	31724-31727	DT	denotes	the
T9302	31728-31737	JJ	denotes	causative
T9303	31738-31744	NN	denotes	allele
T9301	31745-31752	NN	denotes	product
T9304	31752-31753	.	denotes	.
T9305	31753-31831	sentence	denotes	If a second, different allele is present, it is considered a functional null.
T9306	31754-31756	IN	denotes	If
T9308	31757-31758	DT	denotes	a
T9310	31759-31765	JJ	denotes	second
T9311	31765-31767	,	denotes	,
T9312	31767-31776	JJ	denotes	different
T9309	31777-31783	NN	denotes	allele
T9307	31784-31786	VBZ	denotes	is
T9314	31787-31794	JJ	denotes	present
T9315	31794-31796	,	denotes	,
T9316	31796-31798	PRP	denotes	it
T9317	31799-31801	VBZ	denotes	is
T9313	31802-31812	VBN	denotes	considered
T9318	31813-31814	DT	denotes	a
T9320	31815-31825	JJ	denotes	functional
T9319	31826-31830	NN	denotes	null
T9321	31830-31831	.	denotes	.
T9322	31831-31931	sentence	denotes	There is a lack of any correlation between the site of the XPD mutation and the resulting disorder.
T9323	31832-31837	EX	denotes	There
T9324	31838-31840	VBZ	denotes	is
T9325	31841-31842	DT	denotes	a
T9326	31843-31847	NN	denotes	lack
T9327	31848-31850	IN	denotes	of
T9328	31851-31854	DT	denotes	any
T9329	31855-31866	NN	denotes	correlation
T9330	31867-31874	IN	denotes	between
T9331	31875-31878	DT	denotes	the
T9332	31879-31883	NN	denotes	site
T9333	31884-31886	IN	denotes	of
T9334	31887-31890	DT	denotes	the
T9336	31891-31894	NN	denotes	XPD
T9335	31895-31903	NN	denotes	mutation
T9337	31904-31907	CC	denotes	and
T9338	31908-31911	DT	denotes	the
T9340	31912-31921	VBG	denotes	resulting
T9339	31922-31930	NN	denotes	disorder
T9341	31930-31931	.	denotes	.
T9342	31931-32047	sentence	denotes	We propose a biallelic hypothesis for compound heterozygotes in which both alleles can contribute to the phenotype.
T9343	31932-31934	PRP	denotes	We
T9344	31935-31942	VBP	denotes	propose
T9345	31943-31944	DT	denotes	a
T9347	31945-31954	JJ	denotes	biallelic
T9346	31955-31965	NN	denotes	hypothesis
T9348	31966-31969	IN	denotes	for
T9349	31970-31978	NN	denotes	compound
T9350	31979-31992	NNS	denotes	heterozygotes
T9351	31993-31995	IN	denotes	in
T9353	31996-32001	WDT	denotes	which
T9354	32002-32006	DT	denotes	both
T9355	32007-32014	NNS	denotes	alleles
T9356	32015-32018	MD	denotes	can
T9352	32019-32029	VB	denotes	contribute
T9357	32030-32032	IN	denotes	to
T9358	32033-32036	DT	denotes	the
T9359	32037-32046	NN	denotes	phenotype
T9360	32046-32047	.	denotes	.
T9361	32047-32284	sentence	denotes	Examples of compound heterozygous patients in which a second, presumed null allele is likely to contribute to disease outcome are provided above in comparison to corresponding homo- or hemizygous patients with the same causative allele.
T9362	32048-32056	NNS	denotes	Examples
T9364	32057-32059	IN	denotes	of
T9365	32060-32068	NN	denotes	compound
T9367	32069-32081	JJ	denotes	heterozygous
T9366	32082-32090	NNS	denotes	patients
T9368	32091-32093	IN	denotes	in
T9370	32094-32099	WDT	denotes	which
T9371	32100-32101	DT	denotes	a
T9373	32102-32108	JJ	denotes	second
T9374	32108-32110	,	denotes	,
T9375	32110-32118	JJ	denotes	presumed
T9376	32119-32123	JJ	denotes	null
T9372	32124-32130	NN	denotes	allele
T9369	32131-32133	VBZ	denotes	is
T9377	32134-32140	JJ	denotes	likely
T9378	32141-32143	TO	denotes	to
T9379	32144-32154	VB	denotes	contribute
T9380	32155-32157	IN	denotes	to
T9381	32158-32165	NN	denotes	disease
T9382	32166-32173	NN	denotes	outcome
T9383	32174-32177	VBP	denotes	are
T9363	32178-32186	VBN	denotes	provided
T9384	32187-32192	RB	denotes	above
T9385	32193-32195	IN	denotes	in
T9386	32196-32206	NN	denotes	comparison
T9387	32207-32209	IN	denotes	to
T9388	32210-32223	VBG	denotes	corresponding
T9390	32224-32228	AFX	denotes	homo
T9392	32228-32229	HYPH	denotes	-
T9393	32230-32232	CC	denotes	or
T9391	32233-32243	JJ	denotes	hemizygous
T9389	32244-32252	NNS	denotes	patients
T9394	32253-32257	IN	denotes	with
T9395	32258-32261	DT	denotes	the
T9397	32262-32266	JJ	denotes	same
T9398	32267-32276	JJ	denotes	causative
T9396	32277-32283	NN	denotes	allele
T9399	32283-32284	.	denotes	.
T9400	32284-32355	sentence	denotes	Numbers in the schematic of the protein indicate the helicase domains.
T9401	32285-32292	NNS	denotes	Numbers
T9403	32293-32295	IN	denotes	in
T9404	32296-32299	DT	denotes	the
T9405	32300-32309	NN	denotes	schematic
T9406	32310-32312	IN	denotes	of
T9407	32313-32316	DT	denotes	the
T9408	32317-32324	NN	denotes	protein
T9402	32325-32333	VBP	denotes	indicate
T9409	32334-32337	DT	denotes	the
T9411	32338-32346	NN	denotes	helicase
T9410	32347-32354	NNS	denotes	domains
T9412	32354-32355	.	denotes	.
T6041	32357-32366	NN	denotes	Potential
T6042	32367-32369	IN	denotes	of
T6043	32370-32378	VBN	denotes	Combined
T6045	32379-32388	JJ	denotes	Recessive
T6044	32389-32396	NNS	denotes	Alleles
T6046	32397-32399	TO	denotes	to
T6047	32400-32406	VB	denotes	Affect
T6048	32407-32417	JJ	denotes	Phenotypic
T6049	32418-32427	NN	denotes	Diversity
T6050	32428-32430	IN	denotes	in
T6051	32431-32438	NNS	denotes	Mammals
T6052	32438-32547	sentence	denotes	In humans, the clinical relevance of biallelic effects such as interallelic complementation remains unknown.
T6053	32439-32441	IN	denotes	In
T6055	32442-32448	NNS	denotes	humans
T6056	32448-32450	,	denotes	,
T6057	32450-32453	DT	denotes	the
T6059	32454-32462	JJ	denotes	clinical
T6058	32463-32472	NN	denotes	relevance
T6060	32473-32475	IN	denotes	of
T6061	32476-32485	JJ	denotes	biallelic
T6062	32486-32493	NNS	denotes	effects
T6063	32494-32498	JJ	denotes	such
T6064	32499-32501	IN	denotes	as
T6065	32502-32514	JJ	denotes	interallelic
T6066	32515-32530	NN	denotes	complementation
T6054	32531-32538	VBZ	denotes	remains
T6067	32539-32546	JJ	denotes	unknown
T6068	32546-32547	.	denotes	.
T6069	32547-32791	sentence	denotes	Although interallelic complementation between two endogenous mutant alleles has been described in cells from a compound heterozygous patient with methylmalonic acidaemia, no observable effects on disease outcome were noted in the patient [28].
T6070	32548-32556	IN	denotes	Although
T6072	32557-32569	JJ	denotes	interallelic
T6073	32570-32585	NN	denotes	complementation
T6074	32586-32593	IN	denotes	between
T6075	32594-32597	CD	denotes	two
T6077	32598-32608	JJ	denotes	endogenous
T6078	32609-32615	JJ	denotes	mutant
T6076	32616-32623	NNS	denotes	alleles
T6079	32624-32627	VBZ	denotes	has
T6080	32628-32632	VBN	denotes	been
T6071	32633-32642	VBN	denotes	described
T6082	32643-32645	IN	denotes	in
T6083	32646-32651	NNS	denotes	cells
T6084	32652-32656	IN	denotes	from
T6085	32657-32658	DT	denotes	a
T6087	32659-32667	NN	denotes	compound
T6088	32668-32680	JJ	denotes	heterozygous
T6086	32681-32688	NN	denotes	patient
T6089	32689-32693	IN	denotes	with
T6090	32694-32707	JJ	denotes	methylmalonic
T6091	32708-32717	NN	denotes	acidaemia
T6092	32717-32719	,	denotes	,
T6093	32719-32721	DT	denotes	no
T6095	32722-32732	JJ	denotes	observable
T6094	32733-32740	NNS	denotes	effects
T6096	32741-32743	IN	denotes	on
T6097	32744-32751	NN	denotes	disease
T6098	32752-32759	NN	denotes	outcome
T6099	32760-32764	VBD	denotes	were
T6081	32765-32770	VBN	denotes	noted
T6100	32771-32773	IN	denotes	in
T6101	32774-32777	DT	denotes	the
T6102	32778-32785	NN	denotes	patient
T6103	32786-32787	-LRB-	denotes	[
T6104	32787-32789	CD	denotes	28
T6105	32789-32790	-RRB-	denotes	]
T6106	32790-32791	.	denotes	.
T6107	32791-33009	sentence	denotes	Thus, to the best of our knowledge, the amelioration of progeroid features observed here is the first in vivo demonstration in compound heterozygous animals of interallelic complementation relevant to a human disease.
T6108	32792-32796	RB	denotes	Thus
T6110	32796-32798	,	denotes	,
T6111	32798-32800	IN	denotes	to
T6112	32801-32804	DT	denotes	the
T6113	32805-32809	JJS	denotes	best
T6114	32810-32812	IN	denotes	of
T6115	32813-32816	PRP$	denotes	our
T6116	32817-32826	NN	denotes	knowledge
T6117	32826-32828	,	denotes	,
T6118	32828-32831	DT	denotes	the
T6119	32832-32844	NN	denotes	amelioration
T6120	32845-32847	IN	denotes	of
T6121	32848-32857	JJ	denotes	progeroid
T6122	32858-32866	NNS	denotes	features
T6123	32867-32875	VBN	denotes	observed
T6124	32876-32880	RB	denotes	here
T6109	32881-32883	VBZ	denotes	is
T6125	32884-32887	DT	denotes	the
T6127	32888-32893	JJ	denotes	first
T6128	32894-32896	FW	denotes	in
T6129	32897-32901	FW	denotes	vivo
T6126	32902-32915	NN	denotes	demonstration
T6130	32916-32918	IN	denotes	in
T6131	32919-32927	NN	denotes	compound
T6133	32928-32940	JJ	denotes	heterozygous
T6132	32941-32948	NNS	denotes	animals
T6134	32949-32951	IN	denotes	of
T6135	32952-32964	JJ	denotes	interallelic
T6136	32965-32980	NN	denotes	complementation
T6137	32981-32989	JJ	denotes	relevant
T6138	32990-32992	IN	denotes	to
T6139	32993-32994	DT	denotes	a
T6141	32995-33000	JJ	denotes	human
T6140	33001-33008	NN	denotes	disease
T6142	33008-33009	.	denotes	.
T6143	33009-33385	sentence	denotes	Keeping in mind that the ~1,200 alleles known to exist for the CTRF gene implicated in the common autosomal recessive disorder cystic fibrosis alone [29] can theoretically result in ~700,000 different allelic combinations, the potential number of allelic combinations of different recessive mutations and single nucleotide polymorphisms genome-wide is currently incalculable.
T6144	33010-33017	VBG	denotes	Keeping
T6146	33018-33020	IN	denotes	in
T6147	33021-33025	NN	denotes	mind
T6148	33026-33030	IN	denotes	that
T6150	33031-33034	DT	denotes	the
T6152	33035-33036	SYM	denotes	~
T6153	33036-33041	CD	denotes	1,200
T6151	33042-33049	NNS	denotes	alleles
T6154	33050-33055	VBN	denotes	known
T6155	33056-33058	TO	denotes	to
T6156	33059-33064	VB	denotes	exist
T6157	33065-33068	IN	denotes	for
T6158	33069-33072	DT	denotes	the
T6160	33073-33077	NN	denotes	CTRF
T6159	33078-33082	NN	denotes	gene
T6161	33083-33093	VBN	denotes	implicated
T6162	33094-33096	IN	denotes	in
T6163	33097-33100	DT	denotes	the
T6165	33101-33107	JJ	denotes	common
T6166	33108-33117	JJ	denotes	autosomal
T6167	33118-33127	JJ	denotes	recessive
T6164	33128-33136	NN	denotes	disorder
T6168	33137-33143	JJ	denotes	cystic
T6169	33144-33152	NN	denotes	fibrosis
T6170	33153-33158	RB	denotes	alone
T6171	33159-33160	-LRB-	denotes	[
T6172	33160-33162	CD	denotes	29
T6173	33162-33163	-RRB-	denotes	]
T6174	33164-33167	MD	denotes	can
T6175	33168-33181	RB	denotes	theoretically
T6149	33182-33188	VB	denotes	result
T6176	33189-33191	IN	denotes	in
T6177	33192-33193	SYM	denotes	~
T6178	33193-33200	CD	denotes	700,000
T6180	33201-33210	JJ	denotes	different
T6181	33211-33218	JJ	denotes	allelic
T6179	33219-33231	NNS	denotes	combinations
T6182	33231-33233	,	denotes	,
T6183	33233-33236	DT	denotes	the
T6185	33237-33246	JJ	denotes	potential
T6184	33247-33253	NN	denotes	number
T6186	33254-33256	IN	denotes	of
T6187	33257-33264	JJ	denotes	allelic
T6188	33265-33277	NNS	denotes	combinations
T6189	33278-33280	IN	denotes	of
T6190	33281-33290	JJ	denotes	different
T6192	33291-33300	JJ	denotes	recessive
T6191	33301-33310	NNS	denotes	mutations
T6193	33311-33314	CC	denotes	and
T6194	33315-33321	JJ	denotes	single
T6196	33322-33332	NN	denotes	nucleotide
T6195	33333-33346	NNS	denotes	polymorphisms
T6197	33347-33353	NN	denotes	genome
T6199	33353-33354	HYPH	denotes	-
T6198	33354-33358	JJ	denotes	wide
T6145	33359-33361	VBZ	denotes	is
T6200	33362-33371	RB	denotes	currently
T6201	33372-33384	JJ	denotes	incalculable
T6202	33384-33385	.	denotes	.
T6203	33385-33592	sentence	denotes	We suggest biallelic effects as a previously underestimated yet important variable in considering genotype–phenotype relationships from autosomal recessive disease to normal phenotypic diversity in mammals.
T6204	33386-33388	PRP	denotes	We
T6205	33389-33396	VBP	denotes	suggest
T6206	33397-33406	JJ	denotes	biallelic
T6207	33407-33414	NNS	denotes	effects
T6208	33415-33417	IN	denotes	as
T6209	33418-33419	DT	denotes	a
T6211	33420-33430	RB	denotes	previously
T6212	33431-33445	VBN	denotes	underestimated
T6214	33446-33449	RB	denotes	yet
T6213	33450-33459	JJ	denotes	important
T6210	33460-33468	NN	denotes	variable
T6215	33469-33471	IN	denotes	in
T6216	33472-33483	VBG	denotes	considering
T6217	33484-33492	NN	denotes	genotype
T6219	33492-33493	HYPH	denotes	–
T6218	33493-33502	NN	denotes	phenotype
T6220	33503-33516	NNS	denotes	relationships
T6221	33517-33521	IN	denotes	from
T6222	33522-33531	JJ	denotes	autosomal
T6224	33532-33541	JJ	denotes	recessive
T6223	33542-33549	NN	denotes	disease
T6225	33550-33552	IN	denotes	to
T6226	33553-33559	JJ	denotes	normal
T6228	33560-33570	JJ	denotes	phenotypic
T6227	33571-33580	NN	denotes	diversity
T6229	33581-33583	IN	denotes	in
T6230	33584-33591	NNS	denotes	mammals
T6231	33591-33592	.	denotes	.
T6232	33592-33769	sentence	denotes	Extension of the above concept implies that recessive mutations can enter evolutionary selection in F1 provided that the second allele carries a different recessive alteration.
T6233	33593-33602	NN	denotes	Extension
T6235	33603-33605	IN	denotes	of
T6236	33606-33609	DT	denotes	the
T6238	33610-33615	JJ	denotes	above
T6237	33616-33623	NN	denotes	concept
T6234	33624-33631	VBZ	denotes	implies
T6239	33632-33636	IN	denotes	that
T6241	33637-33646	JJ	denotes	recessive
T6242	33647-33656	NNS	denotes	mutations
T6243	33657-33660	MD	denotes	can
T6240	33661-33666	VB	denotes	enter
T6244	33667-33679	JJ	denotes	evolutionary
T6245	33680-33689	NN	denotes	selection
T6246	33690-33692	IN	denotes	in
T6247	33693-33695	NN	denotes	F1
T6248	33696-33704	VBN	denotes	provided
T6249	33705-33709	IN	denotes	that
T6251	33710-33713	DT	denotes	the
T6253	33714-33720	JJ	denotes	second
T6252	33721-33727	NN	denotes	allele
T6250	33728-33735	VBZ	denotes	carries
T6254	33736-33737	DT	denotes	a
T6256	33738-33747	JJ	denotes	different
T6257	33748-33757	JJ	denotes	recessive
T6255	33758-33768	NN	denotes	alteration
T6258	33768-33769	.	denotes	.
T6259	33769-33966	sentence	denotes	Finally, our data highlight the potential of clinically relevant alleles previously designated as null, with little or no detectable expression or activity, to nonetheless contribute to phenotype.
T6260	33770-33777	RB	denotes	Finally
T6262	33777-33779	,	denotes	,
T6263	33779-33782	PRP$	denotes	our
T6264	33783-33787	NNS	denotes	data
T6261	33788-33797	VBP	denotes	highlight
T6265	33798-33801	DT	denotes	the
T6266	33802-33811	NN	denotes	potential
T6267	33812-33814	IN	denotes	of
T6268	33815-33825	RB	denotes	clinically
T6269	33826-33834	JJ	denotes	relevant
T6270	33835-33842	NNS	denotes	alleles
T6271	33843-33853	RB	denotes	previously
T6272	33854-33864	VBN	denotes	designated
T6273	33865-33867	IN	denotes	as
T6274	33868-33872	JJ	denotes	null
T6275	33872-33874	,	denotes	,
T6276	33874-33878	IN	denotes	with
T6277	33879-33885	JJ	denotes	little
T6279	33886-33888	CC	denotes	or
T6280	33889-33891	DT	denotes	no
T6281	33892-33902	JJ	denotes	detectable
T6278	33903-33913	NN	denotes	expression
T6282	33914-33916	CC	denotes	or
T6283	33917-33925	NN	denotes	activity
T6284	33925-33927	,	denotes	,
T6285	33927-33929	TO	denotes	to
T6287	33930-33941	RB	denotes	nonetheless
T6286	33942-33952	VB	denotes	contribute
T6288	33953-33955	IN	denotes	to
T6289	33956-33965	NN	denotes	phenotype
T6290	33965-33966	.	denotes	.
T6364	33991-34001	NN	denotes	Derivation
T6365	34002-34005	CC	denotes	and
T6366	34006-34014	NN	denotes	analysis
T6367	34015-34017	IN	denotes	of
T6368	34018-34024	JJ	denotes	mutant
T6369	34025-34029	NNS	denotes	mice
T6370	34029-34030	.	denotes	.
T6371	34030-34120	sentence	denotes	Generation of XpdTTD (XPDR722W) and XpdTTD/KO mice has been described previously [21,22].
T6372	34031-34041	NN	denotes	Generation
T6374	34042-34044	IN	denotes	of
T6375	34045-34051	NN	denotes	XpdTTD
T6377	34052-34053	-LRB-	denotes	(
T6378	34053-34061	NN	denotes	XPDR722W
T6379	34061-34062	-RRB-	denotes	)
T6380	34063-34066	CC	denotes	and
T6381	34067-34073	NN	denotes	XpdTTD
T6383	34073-34074	HYPH	denotes	/
T6382	34074-34076	NN	denotes	KO
T6376	34077-34081	NNS	denotes	mice
T6384	34082-34085	VBZ	denotes	has
T6385	34086-34090	VBN	denotes	been
T6373	34091-34100	VBN	denotes	described
T6386	34101-34111	RB	denotes	previously
T6387	34112-34113	-LRB-	denotes	[
T6389	34113-34115	CD	denotes	21
T6390	34115-34116	,	denotes	,
T6388	34116-34118	CD	denotes	22
T6391	34118-34119	-RRB-	denotes	]
T6392	34119-34120	.	denotes	.
T6393	34120-34309	sentence	denotes	A detailed description of the generation of targeting constructs for Xpd†XPCS and Xpd †XP alleles carrying mutations encoding the G602D and R683W alterations will be provided upon request.
T6394	34121-34122	DT	denotes	A
T6396	34123-34131	JJ	denotes	detailed
T6395	34132-34143	NN	denotes	description
T6398	34144-34146	IN	denotes	of
T6399	34147-34150	DT	denotes	the
T6400	34151-34161	NN	denotes	generation
T6401	34162-34164	IN	denotes	of
T6402	34165-34174	VBG	denotes	targeting
T6403	34175-34185	NNS	denotes	constructs
T6404	34186-34189	IN	denotes	for
T6405	34190-34198	NN	denotes	Xpd†XPCS
T6407	34199-34202	CC	denotes	and
T6408	34203-34210	NN	denotes	Xpd †XP
T6406	34211-34218	NNS	denotes	alleles
T6409	34219-34227	VBG	denotes	carrying
T6410	34228-34237	NNS	denotes	mutations
T6411	34238-34246	VBG	denotes	encoding
T6412	34247-34250	DT	denotes	the
T6414	34251-34256	NN	denotes	G602D
T6415	34257-34260	CC	denotes	and
T6416	34261-34266	NN	denotes	R683W
T6413	34267-34278	NNS	denotes	alterations
T6417	34279-34283	MD	denotes	will
T6418	34284-34286	VB	denotes	be
T6397	34287-34295	VBN	denotes	provided
T6419	34296-34300	IN	denotes	upon
T6420	34301-34308	NN	denotes	request
T6421	34308-34309	.	denotes	.
T6422	34309-34404	sentence	denotes	Chimeric mice and mouse embryonic fibroblasts were generated according to standard procedures.
T6423	34310-34318	JJ	denotes	Chimeric
T6425	34319-34323	NNS	denotes	mice
T6426	34324-34327	CC	denotes	and
T6427	34328-34333	NN	denotes	mouse
T6428	34334-34343	JJ	denotes	embryonic
T6424	34344-34355	NNS	denotes	fibroblasts
T6430	34356-34360	VBD	denotes	were
T6429	34361-34370	VBN	denotes	generated
T6431	34371-34380	VBG	denotes	according
T6432	34381-34383	IN	denotes	to
T6433	34384-34392	JJ	denotes	standard
T6434	34393-34403	NNS	denotes	procedures
T6435	34403-34404	.	denotes	.
T6436	34404-34484	sentence	denotes	Haematoxylin and eosin staining was performed according to standard procedures.
T6437	34405-34417	NN	denotes	Haematoxylin
T6439	34418-34421	CC	denotes	and
T6440	34422-34427	NN	denotes	eosin
T6438	34428-34436	NN	denotes	staining
T6442	34437-34440	VBD	denotes	was
T6441	34441-34450	VBN	denotes	performed
T6443	34451-34460	VBG	denotes	according
T6444	34461-34463	IN	denotes	to
T6445	34464-34472	JJ	denotes	standard
T6446	34473-34483	NNS	denotes	procedures
T6447	34483-34484	.	denotes	.
T6448	34484-34540	sentence	denotes	Amino acid analysis was conducted as described in [21].
T6449	34485-34490	NN	denotes	Amino
T6450	34491-34495	NN	denotes	acid
T6451	34496-34504	NN	denotes	analysis
T6453	34505-34508	VBD	denotes	was
T6452	34509-34518	VBN	denotes	conducted
T6454	34519-34521	IN	denotes	as
T6455	34522-34531	VBN	denotes	described
T6456	34532-34534	IN	denotes	in
T6457	34535-34536	-LRB-	denotes	[
T6458	34536-34538	CD	denotes	21
T6459	34538-34539	-RRB-	denotes	]
T6460	34539-34540	.	denotes	.
T6461	34540-34637	sentence	denotes	Blood values were analysed using Animal Blood Counter Vet (ABX Diagnostix, Montpellier, France).
T6462	34541-34546	NN	denotes	Blood
T6463	34547-34553	NNS	denotes	values
T6465	34554-34558	VBD	denotes	were
T6464	34559-34567	VBN	denotes	analysed
T6466	34568-34573	VBG	denotes	using
T6467	34574-34580	NN	denotes	Animal
T6469	34581-34586	NN	denotes	Blood
T6470	34587-34594	JJ	denotes	Counter
T6468	34595-34598	NN	denotes	Vet
T6471	34599-34600	-LRB-	denotes	(
T6473	34600-34603	NNP	denotes	ABX
T6472	34604-34614	NNP	denotes	Diagnostix
T6474	34614-34616	,	denotes	,
T6475	34616-34627	NNP	denotes	Montpellier
T6476	34627-34629	,	denotes	,
T6477	34629-34635	NNP	denotes	France
T6478	34635-34636	-RRB-	denotes	)
T6479	34636-34637	.	denotes	.
T6480	34637-34732	sentence	denotes	Radiographs were taken, and relative bone mineral density was calculated as described in [15].
T6481	34638-34649	NNS	denotes	Radiographs
T6483	34650-34654	VBD	denotes	were
T6482	34655-34660	VBN	denotes	taken
T6484	34660-34662	,	denotes	,
T6485	34662-34665	CC	denotes	and
T6486	34666-34674	JJ	denotes	relative
T6488	34675-34679	NN	denotes	bone
T6489	34680-34687	NN	denotes	mineral
T6487	34688-34695	NN	denotes	density
T6491	34696-34699	VBD	denotes	was
T6490	34700-34710	VBN	denotes	calculated
T6492	34711-34713	IN	denotes	as
T6493	34714-34723	VBN	denotes	described
T6494	34724-34726	IN	denotes	in
T6495	34727-34728	-LRB-	denotes	[
T6496	34728-34730	CD	denotes	15
T6497	34730-34731	-RRB-	denotes	]
T6498	34731-34732	.	denotes	.
T6499	34732-34823	sentence	denotes	Mice used in this study were in a 129Ola/C57BL6 mixed background unless noted differently.
T6500	34733-34737	NNS	denotes	Mice
T6502	34738-34742	VBN	denotes	used
T6503	34743-34745	IN	denotes	in
T6504	34746-34750	DT	denotes	this
T6505	34751-34756	NN	denotes	study
T6501	34757-34761	VBD	denotes	were
T6506	34762-34764	IN	denotes	in
T6507	34765-34766	DT	denotes	a
T6509	34767-34773	NN	denotes	129Ola
T6511	34773-34774	HYPH	denotes	/
T6510	34774-34780	NN	denotes	C57BL6
T6512	34781-34786	JJ	denotes	mixed
T6508	34787-34797	NN	denotes	background
T6513	34798-34804	IN	denotes	unless
T6514	34805-34810	VBN	denotes	noted
T6515	34811-34822	RB	denotes	differently
T6516	34822-34823	.	denotes	.
T6517	34823-35050	sentence	denotes	All experiments involving mice were judged and approved by the national committee for genetic identification of organisms and the animal ethical committee, and were conducted according to national and international guidelines.
T6518	34824-34827	DT	denotes	All
T6519	34828-34839	NNS	denotes	experiments
T6521	34840-34849	VBG	denotes	involving
T6522	34850-34854	NNS	denotes	mice
T6523	34855-34859	VBD	denotes	were
T6520	34860-34866	VBN	denotes	judged
T6524	34867-34870	CC	denotes	and
T6525	34871-34879	VBN	denotes	approved
T6526	34880-34882	IN	denotes	by
T6527	34883-34886	DT	denotes	the
T6529	34887-34895	JJ	denotes	national
T6528	34896-34905	NN	denotes	committee
T6530	34906-34909	IN	denotes	for
T6531	34910-34917	JJ	denotes	genetic
T6532	34918-34932	NN	denotes	identification
T6533	34933-34935	IN	denotes	of
T6534	34936-34945	NNS	denotes	organisms
T6535	34946-34949	CC	denotes	and
T6536	34950-34953	DT	denotes	the
T6538	34954-34960	NN	denotes	animal
T6539	34961-34968	JJ	denotes	ethical
T6537	34969-34978	NN	denotes	committee
T6540	34978-34980	,	denotes	,
T6541	34980-34983	CC	denotes	and
T6542	34984-34988	VBD	denotes	were
T6543	34989-34998	VBN	denotes	conducted
T6544	34999-35008	VBG	denotes	according
T6545	35009-35011	IN	denotes	to
T6546	35012-35020	JJ	denotes	national
T6548	35021-35024	CC	denotes	and
T6549	35025-35038	JJ	denotes	international
T6547	35039-35049	NNS	denotes	guidelines
T6550	35049-35050	.	denotes	.
T6587	35052-35054	NN	denotes	UV
T6588	35055-35066	NN	denotes	sensitivity
T6589	35066-35068	,	denotes	,
T6590	35068-35070	NN	denotes	UV
T6592	35070-35071	HYPH	denotes	-
T6591	35071-35074	NN	denotes	UDS
T6594	35074-35076	,	denotes	,
T6595	35076-35078	NN	denotes	UV
T6597	35078-35079	HYPH	denotes	-
T6596	35079-35082	NN	denotes	RRS
T6598	35082-35084	,	denotes	,
T6599	35084-35087	CC	denotes	and
T6600	35088-35093	NN	denotes	TFIIH
T6601	35094-35102	NN	denotes	incision
T6603	35102-35103	HYPH	denotes	/
T6602	35103-35111	NN	denotes	excision
T6593	35112-35120	NN	denotes	activity
T6604	35120-35121	.	denotes	.
T6605	35121-35208	sentence	denotes	UV survival, UV-UDS, and UV-RRS assays were performed as described previously [21,30].
T6606	35122-35124	NN	denotes	UV
T6607	35125-35133	NN	denotes	survival
T6609	35133-35135	,	denotes	,
T6610	35135-35137	NN	denotes	UV
T6612	35137-35138	HYPH	denotes	-
T6611	35138-35141	NN	denotes	UDS
T6613	35141-35143	,	denotes	,
T6614	35143-35146	CC	denotes	and
T6615	35147-35149	NN	denotes	UV
T6617	35149-35150	HYPH	denotes	-
T6616	35150-35153	NN	denotes	RRS
T6608	35154-35160	NNS	denotes	assays
T6619	35161-35165	VBD	denotes	were
T6618	35166-35175	VBN	denotes	performed
T6620	35176-35178	IN	denotes	as
T6621	35179-35188	VBN	denotes	described
T6622	35189-35199	RB	denotes	previously
T6623	35200-35201	-LRB-	denotes	[
T6625	35201-35203	CD	denotes	21
T6626	35203-35204	,	denotes	,
T6624	35204-35206	CD	denotes	30
T6627	35206-35207	-RRB-	denotes	]
T6628	35207-35208	.	denotes	.
T6629	35208-35367	sentence	denotes	For UV-RRS, average values from the representative experiment containing two wt, three XpdTTD/TTD, two XpdTTD/XPCS, and one XpdTTD/XP cell line are presented.
T6630	35209-35212	IN	denotes	For
T6632	35213-35215	NN	denotes	UV
T6634	35215-35216	HYPH	denotes	-
T6633	35216-35219	NN	denotes	RRS
T6635	35219-35221	,	denotes	,
T6636	35221-35228	JJ	denotes	average
T6637	35229-35235	NNS	denotes	values
T6638	35236-35240	IN	denotes	from
T6639	35241-35244	DT	denotes	the
T6641	35245-35259	JJ	denotes	representative
T6640	35260-35270	NN	denotes	experiment
T6642	35271-35281	VBG	denotes	containing
T6643	35282-35285	CD	denotes	two
T6644	35286-35288	NN	denotes	wt
T6646	35288-35290	,	denotes	,
T6647	35290-35295	CD	denotes	three
T6649	35296-35302	NN	denotes	XpdTTD
T6650	35302-35303	HYPH	denotes	/
T6648	35303-35306	NN	denotes	TTD
T6651	35306-35308	,	denotes	,
T6652	35308-35311	CD	denotes	two
T6654	35312-35318	NN	denotes	XpdTTD
T6655	35318-35319	HYPH	denotes	/
T6653	35319-35323	NN	denotes	XPCS
T6656	35323-35325	,	denotes	,
T6657	35325-35328	CC	denotes	and
T6658	35329-35332	CD	denotes	one
T6660	35333-35339	NN	denotes	XpdTTD
T6661	35339-35340	HYPH	denotes	/
T6659	35340-35342	NN	denotes	XP
T6662	35343-35347	NN	denotes	cell
T6645	35348-35352	NN	denotes	line
T6663	35353-35356	VBP	denotes	are
T6631	35357-35366	VBN	denotes	presented
T6664	35366-35367	.	denotes	.
T6665	35367-35615	sentence	denotes	The ~48% UV-UDS value presented in this study for XpdTTD/TTD cells differs from our previously published data of 25% UV-UDS [21], possibly because of the high variability intrinsic to the assay or routine variations in the cell culture conditions.
T6666	35368-35371	DT	denotes	The
T6668	35372-35373	SYM	denotes	~
T6669	35373-35375	CD	denotes	48
T6670	35375-35376	NN	denotes	%
T6671	35377-35379	NN	denotes	UV
T6673	35379-35380	HYPH	denotes	-
T6672	35380-35383	NN	denotes	UDS
T6667	35384-35389	NN	denotes	value
T6675	35390-35399	VBN	denotes	presented
T6676	35400-35402	IN	denotes	in
T6677	35403-35407	DT	denotes	this
T6678	35408-35413	NN	denotes	study
T6679	35414-35417	IN	denotes	for
T6680	35418-35424	NN	denotes	XpdTTD
T6682	35424-35425	HYPH	denotes	/
T6681	35425-35428	NN	denotes	TTD
T6683	35429-35434	NNS	denotes	cells
T6674	35435-35442	VBZ	denotes	differs
T6684	35443-35447	IN	denotes	from
T6685	35448-35451	PRP$	denotes	our
T6687	35452-35462	RB	denotes	previously
T6688	35463-35472	VBN	denotes	published
T6686	35473-35477	NNS	denotes	data
T6689	35478-35480	IN	denotes	of
T6690	35481-35483	CD	denotes	25
T6691	35483-35484	NN	denotes	%
T6693	35485-35487	NN	denotes	UV
T6694	35487-35488	HYPH	denotes	-
T6692	35488-35491	NN	denotes	UDS
T6695	35492-35493	-LRB-	denotes	[
T6696	35493-35495	CD	denotes	21
T6697	35495-35496	-RRB-	denotes	]
T6698	35496-35498	,	denotes	,
T6699	35498-35506	RB	denotes	possibly
T6700	35507-35514	IN	denotes	because
T6701	35515-35517	IN	denotes	of
T6702	35518-35521	DT	denotes	the
T6704	35522-35526	JJ	denotes	high
T6703	35527-35538	NN	denotes	variability
T6705	35539-35548	JJ	denotes	intrinsic
T6706	35549-35551	IN	denotes	to
T6707	35552-35555	DT	denotes	the
T6708	35556-35561	NN	denotes	assay
T6709	35562-35564	CC	denotes	or
T6710	35565-35572	JJ	denotes	routine
T6711	35573-35583	NNS	denotes	variations
T6712	35584-35586	IN	denotes	in
T6713	35587-35590	DT	denotes	the
T6715	35591-35595	NN	denotes	cell
T6716	35596-35603	NN	denotes	culture
T6714	35604-35614	NNS	denotes	conditions
T6717	35614-35615	.	denotes	.
T6718	35615-35730	sentence	denotes	For the incision/excision activity assay, recombinant TFIIH was prepared and assayed as described previously [27].
T6719	35616-35619	IN	denotes	For
T6721	35620-35623	DT	denotes	the
T6723	35624-35632	NN	denotes	incision
T6725	35632-35633	HYPH	denotes	/
T6724	35633-35641	NN	denotes	excision
T6726	35642-35650	NN	denotes	activity
T6722	35651-35656	NN	denotes	assay
T6727	35656-35658	,	denotes	,
T6728	35658-35669	JJ	denotes	recombinant
T6729	35670-35675	NN	denotes	TFIIH
T6730	35676-35679	VBD	denotes	was
T6720	35680-35688	VBN	denotes	prepared
T6731	35689-35692	CC	denotes	and
T6732	35693-35700	VBN	denotes	assayed
T6733	35701-35703	IN	denotes	as
T6734	35704-35713	VBN	denotes	described
T6735	35714-35724	RB	denotes	previously
T6736	35725-35726	-LRB-	denotes	[
T6737	35726-35728	CD	denotes	27
T6738	35728-35729	-RRB-	denotes	]
T6739	35729-35730	.	denotes	.
T6770	35732-35743	JJ	denotes	Comparative
T6771	35744-35762	NN	denotes	immunofluorescence
T6772	35762-35763	.	denotes	.
T6773	35763-35965	sentence	denotes	Latex bead labelling and comparative immunofluorescence analysis of the p62 subunit of the TFIIH was performed as described previously [16,17] using primary mouse embryonic fibroblasts at passages 2–5.
T6774	35764-35769	NN	denotes	Latex
T6776	35770-35774	NN	denotes	bead
T6775	35775-35784	NN	denotes	labelling
T6778	35785-35788	CC	denotes	and
T6779	35789-35800	JJ	denotes	comparative
T6781	35801-35819	NN	denotes	immunofluorescence
T6780	35820-35828	NN	denotes	analysis
T6782	35829-35831	IN	denotes	of
T6783	35832-35835	DT	denotes	the
T6785	35836-35839	NN	denotes	p62
T6784	35840-35847	NN	denotes	subunit
T6786	35848-35850	IN	denotes	of
T6787	35851-35854	DT	denotes	the
T6788	35855-35860	NN	denotes	TFIIH
T6789	35861-35864	VBD	denotes	was
T6777	35865-35874	VBN	denotes	performed
T6790	35875-35877	IN	denotes	as
T6791	35878-35887	VBN	denotes	described
T6792	35888-35898	RB	denotes	previously
T6793	35899-35900	-LRB-	denotes	[
T6795	35900-35902	CD	denotes	16
T6796	35902-35903	,	denotes	,
T6794	35903-35905	CD	denotes	17
T6797	35905-35906	-RRB-	denotes	]
T6798	35907-35912	VBG	denotes	using
T6799	35913-35920	JJ	denotes	primary
T6801	35921-35926	NN	denotes	mouse
T6802	35927-35936	JJ	denotes	embryonic
T6800	35937-35948	NNS	denotes	fibroblasts
T6803	35949-35951	IN	denotes	at
T6804	35952-35960	NNS	denotes	passages
T6805	35961-35962	CD	denotes	2
T6806	35962-35963	SYM	denotes	–
T6807	35963-35964	CD	denotes	5
T6808	35964-35965	.	denotes	.
T6809	35965-36162	sentence	denotes	Two or more cell lines per genotype (except for the XpdTTD/†XP cells, in which only one cell line was used in repeated experiments) were used, and experiments were repeated 2–6 times per genotype.
T6810	35966-35969	CD	denotes	Two
T6812	35970-35972	CC	denotes	or
T6813	35973-35977	JJR	denotes	more
T6814	35978-35982	NN	denotes	cell
T6811	35983-35988	NNS	denotes	lines
T6816	35989-35992	IN	denotes	per
T6817	35993-36001	NN	denotes	genotype
T6818	36002-36003	-LRB-	denotes	(
T6819	36003-36009	IN	denotes	except
T6820	36010-36013	IN	denotes	for
T6821	36014-36017	DT	denotes	the
T6823	36018-36024	NN	denotes	XpdTTD
T6825	36024-36025	HYPH	denotes	/
T6824	36025-36028	NN	denotes	†XP
T6822	36029-36034	NNS	denotes	cells
T6826	36034-36036	,	denotes	,
T6827	36036-36038	IN	denotes	in
T6829	36039-36044	WDT	denotes	which
T6830	36045-36049	RB	denotes	only
T6832	36050-36053	CD	denotes	one
T6833	36054-36058	NN	denotes	cell
T6831	36059-36063	NN	denotes	line
T6834	36064-36067	VBD	denotes	was
T6828	36068-36072	VBN	denotes	used
T6835	36073-36075	IN	denotes	in
T6836	36076-36084	VBN	denotes	repeated
T6837	36085-36096	NNS	denotes	experiments
T6838	36096-36097	-RRB-	denotes	)
T6839	36098-36102	VBD	denotes	were
T6815	36103-36107	VBN	denotes	used
T6840	36107-36109	,	denotes	,
T6841	36109-36112	CC	denotes	and
T6842	36113-36124	NNS	denotes	experiments
T6844	36125-36129	VBD	denotes	were
T6843	36130-36138	VBN	denotes	repeated
T6845	36139-36140	CD	denotes	2
T6847	36140-36141	HYPH	denotes	–
T6846	36141-36142	CD	denotes	6
T6848	36143-36148	NNS	denotes	times
T6849	36149-36152	IN	denotes	per
T6850	36153-36161	NN	denotes	genotype
T6851	36161-36162	.	denotes	.
R1	T86	T84	prep	of,Rescue
R10	T96	T97	mark	Although,is
R100	T193	T191	pobj	repair,in
R1000	T1496	T1497	mark	Because,was
R1001	T1497	T1500	advcl	was,expected
R1002	T1498	T1499	compound	patient,XPCS2
R1003	T1499	T1497	nsubj	XPCS2,was
R1004	T1501	T1502	det	a,hemizygote
R1005	T1502	T1497	attr	hemizygote,was
R1006	T1503	T1502	prep	with,hemizygote
R1007	T1504	T1505	amod	mutant,protein
R1008	T1505	T1503	pobj	protein,with
R1009	T1506	T1505	compound	XPD,protein
R101	T194	T193	compound	DNA,repair
R1010	T1507	T1508	punct	(,XPDG602D
R1011	T1508	T1505	parataxis	XPDG602D,protein
R1012	T1509	T1508	punct	),XPDG602D
R1013	T1510	T1505	acl	expressed,protein
R1014	T1511	T1510	prep	from,expressed
R1015	T1512	T1513	det	a,allele
R1016	T1513	T1511	pobj	allele,from
R1017	T1514	T1513	amod	single,allele
R1018	T1515	T1500	punct	", ",expected
R1019	T1516	T1517	det	the,mutation
R102	T195	T193	cc	and,repair
R1020	T1517	T1500	nsubjpass	mutation,expected
R1021	T1518	T1517	amod	corresponding,mutation
R1022	T1519	T1500	auxpass	was,expected
R1023	T1520	T1521	aux	to,be
R1024	T1521	T1500	xcomp	be,expected
R1025	T1522	T1521	acomp	viable,be
R1026	T1523	T1521	prep	in,be
R1027	T1524	T1525	det	the,state
R1028	T1525	T1523	pobj	state,in
R1029	T1526	T1525	amod	homozygous,state
R103	T196	T197	amod	basal,transcription
R1030	T1527	T1500	punct	.,expected
R1031	T1529	T1530	advmod	However,observed
R1032	T1531	T1530	punct	", ",observed
R1033	T1532	T1533	amod	homozygous,mice
R1034	T1533	T1530	nsubjpass	mice,observed
R1035	T1534	T1533	amod	mutant,mice
R1036	T1535	T1530	auxpass	were,observed
R1037	T1536	T1530	neg	not,observed
R1038	T1537	T1530	punct	", ",observed
R1039	T1538	T1539	preconj	neither,amongst
R104	T197	T193	conj	transcription,repair
R1040	T1539	T1530	prep	amongst,observed
R1041	T1540	T1541	amod	live,births
R1042	T1541	T1539	pobj	births,amongst
R1043	T1542	T1541	cc	nor,births
R1044	T1543	T1544	amod	embryonic,day
R1045	T1544	T1545	nmod	day,embryos
R1046	T1545	T1541	conj	embryos,births
R1047	T1546	T1544	nummod	13.5,day
R1048	T1547	T1544	punct	(,day
R1049	T1548	T1544	appos	E13.5,day
R105	T198	T183	punct	", ",result
R1050	T1549	T1544	punct	),day
R1051	T1550	T1544	cc	or,day
R1052	T1551	T1544	conj	E3.5,day
R1053	T1552	T1553	punct	(,Table
R1054	T1553	T1530	parataxis	Table,observed
R1055	T1554	T1553	nummod	1,Table
R1056	T1555	T1553	punct	),Table
R1057	T1556	T1530	punct	.,observed
R1058	T1558	T1559	det	The,allele
R1059	T1559	T1564	nsubjpass	allele,designated
R106	T199	T183	prep	in,result
R1060	T1560	T1559	amod	corresponding,allele
R1061	T1561	T1559	amod	hypomorphic,allele
R1062	T1562	T1559	punct	", ",allele
R1063	T1563	T1559	amod	mutant,allele
R1064	T1565	T1564	auxpass	was,designated
R1065	T1566	T1564	advmod	thus,designated
R1066	T1567	T1564	prep	as,designated
R1067	T1568	T1569	amod	homozygous,lethal
R1068	T1569	T1567	pobj	lethal,as
R1069	T1570	T1571	punct	(,†XPCS
R107	T200	T201	amod	diverse,pathologies
R1070	T1571	T1569	parataxis	†XPCS,lethal
R1071	T1572	T1571	punct	),†XPCS
R1072	T1573	T1564	punct	.,designated
R1073	T1575	T1576	amod	Homozygous,lethality
R1074	T1576	T1577	nsubj	lethality,is
R1075	T1578	T1576	prep	of,lethality
R1076	T1579	T1580	det	the,allele
R1077	T1580	T1578	pobj	allele,of
R1078	T1581	T1580	compound	XPCS,allele
R1079	T1582	T1583	advmod	likely,due
R108	T201	T199	pobj	pathologies,in
R1080	T1583	T1577	prep	due,is
R1081	T1584	T1583	prep	to,due
R1082	T1585	T1586	amod	reduced,levels
R1083	T1586	T1584	pobj	levels,to
R1084	T1587	T1586	prep	of,levels
R1085	T1588	T1587	pobj	expression,of
R1086	T1589	T1588	prep	of,expression
R1087	T1590	T1591	det	this,protein
R1088	T1591	T1589	pobj	protein,of
R1089	T1592	T1591	amod	essential,protein
R109	T202	T201	acl	ranging,pathologies
R1090	T1593	T1586	prep	as,levels
R1091	T1594	T1595	det	a,result
R1092	T1595	T1593	pobj	result,as
R1093	T1596	T1595	prep	of,result
R1094	T1597	T1598	compound	gene,targeting
R1095	T1598	T1596	pobj	targeting,of
R1096	T1599	T1600	punct	(,1A
R1097	T1600	T1598	parataxis	1A,targeting
R1098	T1601	T1600	compound	Figure,1A
R1099	T1602	T1600	punct	),1A
R11	T97	T114	advcl	is,documented
R110	T203	T202	prep	from,ranging
R1100	T1603	T1604	amod	rather,than
R1101	T1604	T1584	cc	than,to
R1102	T1605	T1584	conj	to,to
R1103	T1606	T1607	det	the,mutation
R1104	T1607	T1605	pobj	mutation,to
R1105	T1608	T1607	appos	itself,mutation
R1106	T1609	T1577	punct	.,is
R1107	T1611	T1612	compound	Xpd,ablation
R1108	T1612	T1613	nsubj	ablation,is
R1109	T1614	T1615	punct	(,KO
R111	T204	T205	amod	elevated,sensitivity
R1110	T1615	T1612	parataxis	KO,ablation
R1111	T1616	T1615	compound	XpdKO,KO
R1112	T1617	T1615	punct	/,KO
R1113	T1618	T1615	punct	),KO
R1114	T1619	T1620	advmod	similarly,incompatible
R1115	T1620	T1613	acomp	incompatible,is
R1116	T1621	T1620	prep	with,incompatible
R1117	T1622	T1621	pobj	life,with
R1118	T1623	T1622	prep	beyond,life
R1119	T1624	T1625	det	the,stages
R112	T205	T203	pobj	sensitivity,from
R1120	T1625	T1623	pobj	stages,beyond
R1121	T1626	T1625	amod	earliest,stages
R1122	T1627	T1625	prep	of,stages
R1123	T1628	T1627	pobj	embryogenesis,of
R1124	T1629	T1630	punct	[,22
R1125	T1630	T1613	parataxis	22,is
R1126	T1631	T1630	punct	],22
R1127	T1632	T1613	punct	.,is
R1128	T1634	T1635	advcl	Consistent,was
R1129	T1636	T1634	prep	with,Consistent
R113	T206	T205	compound	UV,sensitivity
R1130	T1637	T1638	det	this,interpretation
R1131	T1638	T1636	pobj	interpretation,with
R1132	T1639	T1635	punct	", ",was
R1133	T1640	T1641	det	a,mutation
R1134	T1641	T1635	nsubj	mutation,was
R1135	T1642	T1641	amod	different,mutation
R1136	T1643	T1641	amod	targeted,mutation
R1137	T1644	T1641	compound	Xpd,mutation
R1138	T1645	T1641	acl	encoding,mutation
R1139	T1646	T1645	dobj	XPDR683W,encoding
R114	T207	T205	cc	and,sensitivity
R1140	T1647	T1646	punct	", ",XPDR683W
R1141	T1648	T1649	dep	which,associated
R1142	T1649	T1646	relcl	associated,XPDR683W
R1143	T1650	T1649	auxpass	is,associated
R1144	T1651	T1649	prep	with,associated
R1145	T1652	T1651	pobj	XP,with
R1146	T1653	T1649	prep	in,associated
R1147	T1654	T1655	det	the,state
R1148	T1655	T1653	pobj	state,in
R1149	T1656	T1655	amod	homozygous,state
R115	T208	T209	compound	cancer,predisposition
R1150	T1657	T1649	prep	in,associated
R1151	T1658	T1657	pobj	humans,in
R1152	T1659	T1635	punct	", ",was
R1153	T1660	T1661	advmod	similarly,underexpressed
R1154	T1661	T1635	acomp	underexpressed,was
R1155	T1662	T1661	cc	and,underexpressed
R1156	T1663	T1661	conj	lethal,underexpressed
R1157	T1664	T1635	prep	in,was
R1158	T1665	T1666	det	the,state
R1159	T1666	T1664	pobj	state,in
R116	T209	T205	conj	predisposition,sensitivity
R1160	T1667	T1666	amod	homozygous,state
R1161	T1668	T1669	punct	(,designated
R1162	T1669	T1635	parataxis	designated,was
R1163	T1670	T1669	prep	as,designated
R1164	T1671	T1672	compound	†XP,allele
R1165	T1672	T1670	pobj	allele,as
R1166	T1673	T1669	punct	),designated
R1167	T1674	T1675	punct	(,1A
R1168	T1675	T1635	parataxis	1A,was
R1169	T1676	T1675	compound	Figure,1A
R117	T210	T203	prep	to,from
R1170	T1677	T1678	punct	–,1C
R1171	T1678	T1675	prep	1C,1A
R1172	T1679	T1675	punct	;,1A
R1173	T1680	T1675	appos	Table,1A
R1174	T1681	T1680	nummod	1,Table
R1175	T1682	T1675	punct	;,1A
R1176	T1683	T1684	amod	unpublished,data
R1177	T1684	T1675	appos	data,1A
R1178	T1685	T1675	punct	),1A
R1179	T1686	T1635	punct	.,was
R118	T211	T212	amod	accelerated,progeria
R1180	T1688	T1689	advmod	Also,resulted
R1181	T1690	T1689	punct	", ",resulted
R1182	T1691	T1692	det	a,approach
R1183	T1692	T1689	nsubj	approach,resulted
R1184	T1693	T1692	amod	different,approach
R1185	T1694	T1692	compound	targeting,approach
R1186	T1695	T1692	acl	leading,approach
R1187	T1696	T1695	prep	to,leading
R1188	T1697	T1698	det	the,use
R1189	T1698	T1696	pobj	use,to
R119	T212	T210	pobj	progeria,to
R1190	T1699	T1698	prep	of,use
R1191	T1700	T1701	det	the,UTR
R1192	T1701	T1699	pobj	UTR,of
R1193	T1702	T1701	amod	native,UTR
R1194	T1703	T1701	nummod	3,UTR
R1195	T1704	T1703	punct	′,3
R1196	T1705	T1698	cc	and,use
R1197	T1706	T1698	conj	removal,use
R1198	T1707	T1706	prep	of,removal
R1199	T1708	T1709	det	the,gene
R12	T98	T99	compound	compound,heterozygosity
R120	T213	T212	amod	segmental,progeria
R1200	T1709	T1707	pobj	gene,of
R1201	T1710	T1709	compound	neo,gene
R1202	T1711	T1689	prep	in,resulted
R1203	T1712	T1711	pobj	normalisation,in
R1204	T1713	T1712	prep	of,normalisation
R1205	T1714	T1715	compound	XpdXPCS,levels
R1206	T1715	T1713	pobj	levels,of
R1207	T1716	T1715	compound	mRNA,levels
R1208	T1717	T1712	cc	and,normalisation
R1209	T1718	T1719	amod	viable,animals
R121	T214	T183	punct	.,result
R1210	T1719	T1712	conj	animals,normalisation
R1211	T1720	T1719	amod	homozygous,animals
R1212	T1721	T1722	nmod	XpdXPCS,XPCS
R1213	T1722	T1719	nmod	XPCS,animals
R1214	T1723	T1722	punct	/,XPCS
R1215	T1724	T1725	punct	(,G602D
R1216	T1725	T1722	parataxis	G602D,XPCS
R1217	T1726	T1725	compound	XPDG602D,G602D
R1218	T1727	T1725	punct	/,G602D
R1219	T1728	T1725	punct	),G602D
R122	T216	T217	nsubj	We,report
R1220	T1729	T1730	punct	[,23
R1221	T1730	T1689	parataxis	23,resulted
R1222	T1731	T1730	punct	],23
R1223	T1732	T1689	punct	.,resulted
R1226	T1954	T1955	punct	“,Allele
R1227	T1955	T1958	nsubj	Allele,Alleviate
R1228	T1956	T1955	amod	Null,Allele
R1229	T1957	T1955	punct	”,Allele
R123	T218	T219	det	a,variety
R1230	T1959	T1958	aux	Can,Alleviate
R1231	T1960	T1961	amod	Developmental,Delay
R1232	T1961	T1958	dobj	Delay,Alleviate
R1233	T1962	T1961	punct	", ",Delay
R1234	T1963	T1964	nmod	Skin,Features
R1235	T1964	T1961	appos	Features,Delay
R1236	T1965	T1963	punct	", ",Skin
R1237	T1966	T1963	cc	and,Skin
R1238	T1967	T1963	conj	Hair,Skin
R1239	T1968	T1964	prep	of,Features
R124	T219	T217	dobj	variety,report
R1240	T1969	T1968	pobj	TTD,of
R1241	T1971	T1972	aux	To,test
R1242	T1972	T1973	advcl	test,combined
R1243	T1974	T1975	det	the,potential
R1244	T1975	T1972	dobj	potential,test
R1245	T1976	T1975	prep	of,potential
R1246	T1977	T1978	det	a,allele
R1247	T1978	T1976	pobj	allele,of
R1248	T1979	T1978	amod	homozygous,allele
R1249	T1980	T1978	amod	lethal,allele
R125	T220	T219	prep	of,variety
R1250	T1981	T1978	punct	“,allele
R1251	T1982	T1978	amod	null,allele
R1252	T1983	T1978	punct	”,allele
R1253	T1984	T1985	aux	to,contribute
R1254	T1985	T1975	acl	contribute,potential
R1255	T1986	T1985	advmod	nevertheless,contribute
R1256	T1987	T1985	prep	to,contribute
R1257	T1988	T1989	amod	organismal,phenotype
R1258	T1989	T1987	pobj	phenotype,to
R1259	T1990	T1973	punct	", ",combined
R126	T221	T222	amod	biallelic,effects
R1260	T1991	T1973	nsubj	we,combined
R1261	T1992	T1993	det	an,allele
R1262	T1993	T1973	dobj	allele,combined
R1263	T1994	T1993	compound	Xpd†XPCS,allele
R1264	T1995	T1993	prep	with,allele
R1265	T1996	T1997	det	a,allele
R1266	T1997	T1995	pobj	allele,with
R1267	T1998	T1997	amod	viable,allele
R1268	T1999	T1997	compound	XpdTTD,allele
R1269	T2000	T1973	prep	by,combined
R127	T222	T220	pobj	effects,of
R1270	T2001	T2000	pcomp	crossing,by
R1271	T2002	T2003	det	the,animals
R1272	T2003	T2001	dobj	animals,crossing
R1273	T2004	T2003	amod	corresponding,animals
R1274	T2005	T2003	amod	heterozygous,animals
R1275	T2006	T1973	punct	.,combined
R1276	T2008	T2009	advcl	Similar,born
R1277	T2010	T2008	prep	to,Similar
R1278	T2011	T2012	amod	hemizygous,mice
R1279	T2012	T2010	pobj	mice,to
R128	T223	T222	prep	on,effects
R1280	T2013	T2012	compound	TTD,mice
R1281	T2014	T2012	acl	carrying,mice
R1282	T2015	T2016	nummod	one,allele
R1283	T2016	T2014	dobj	allele,carrying
R1284	T2017	T2016	amod	true,allele
R1285	T2018	T2019	compound	Xpd,knockout
R1286	T2019	T2016	compound	knockout,allele
R1287	T2020	T2021	punct	(,KO
R1288	T2021	T2016	parataxis	KO,allele
R1289	T2022	T2021	compound	XpdTTD,KO
R129	T224	T225	amod	organismal,phenotype
R1290	T2023	T2021	punct	/,KO
R1291	T2024	T2021	punct	),KO
R1292	T2025	T2009	punct	", ",born
R1293	T2026	T2027	nmod	compound,mice
R1294	T2027	T2009	nsubjpass	mice,born
R1295	T2028	T2027	amod	heterozygous,mice
R1296	T2029	T2030	compound	XpdTTD,†XPCS
R1297	T2030	T2027	compound	†XPCS,mice
R1298	T2031	T2030	punct	/,†XPCS
R1299	T2032	T2009	auxpass	were,born
R13	T99	T97	nsubj	heterozygosity,is
R130	T225	T223	pobj	phenotype,on
R1300	T2033	T2009	prep	at,born
R1301	T2034	T2035	det	the,frequencies
R1302	T2035	T2033	pobj	frequencies,at
R1303	T2036	T2035	amod	expected,frequencies
R1304	T2037	T2035	amod	Mendelian,frequencies
R1305	T2038	T2009	punct	.,born
R1306	T2040	T2041	nsubjpass	Expression,reduced
R1307	T2042	T2040	prep	from,Expression
R1308	T2043	T2044	det	the,allele
R1309	T2044	T2042	pobj	allele,from
R131	T226	T222	amod	attributable,effects
R1310	T2045	T2044	compound	Xpd†XPCS,allele
R1311	T2046	T2041	auxpass	was,reduced
R1312	T2047	T2041	advmod	also,reduced
R1313	T2048	T2041	prep	in,reduced
R1314	T2049	T2050	det	the,testis
R1315	T2050	T2048	pobj	testis,in
R1316	T2051	T2050	prep	of,testis
R1317	T2052	T2053	nmod	compound,animals
R1318	T2053	T2051	pobj	animals,of
R1319	T2054	T2053	amod	heterozygous,animals
R132	T227	T226	prep	to,attributable
R1320	T2055	T2041	punct	", ",reduced
R1321	T2056	T2057	mark	whereas,increased
R1322	T2057	T2041	advcl	increased,reduced
R1323	T2058	T2057	nsubjpass	expression,increased
R1324	T2059	T2058	prep	from,expression
R1325	T2060	T2061	det	the,allele
R1326	T2061	T2059	pobj	allele,from
R1327	T2062	T2061	compound	XpdTTD,allele
R1328	T2063	T2057	auxpass	was,increased
R1329	T2064	T2057	advcl	relative,increased
R133	T228	T227	pobj	combinations,to
R1330	T2065	T2064	prep	to,relative
R1331	T2066	T2065	pobj	wt,to
R1332	T2067	T2057	prep	by,increased
R1333	T2068	T2069	punct	~,5-fold
R1334	T2069	T2067	pobj	5-fold,by
R1335	T2070	T2071	punct	(,1E
R1336	T2071	T2057	parataxis	1E,increased
R1337	T2072	T2071	compound	Figure,1E
R1338	T2073	T2071	punct	),1E
R1339	T2074	T2041	punct	.,reduced
R134	T229	T228	prep	of,combinations
R1340	T2076	T2077	prep	Because,were
R1341	T2078	T2076	pcomp	of,Because
R1342	T2079	T2080	det	a,lack
R1343	T2080	T2076	pobj	lack,Because
R1344	T2081	T2080	prep	of,lack
R1345	T2082	T2083	amod	available,antibodies
R1346	T2083	T2081	pobj	antibodies,of
R1347	T2084	T2083	cc	and,antibodies
R1348	T2085	T2086	det	the,inability
R1349	T2086	T2083	conj	inability,antibodies
R135	T230	T231	amod	recessive,alleles
R1350	T2087	T2088	aux	to,distinguish
R1351	T2088	T2086	acl	distinguish,inability
R1352	T2089	T2088	prep	amongst,distinguish
R1353	T2090	T2091	amod	various,forms
R1354	T2091	T2089	pobj	forms,amongst
R1355	T2092	T2091	amod	mutant,forms
R1356	T2093	T2091	prep	of,forms
R1357	T2094	T2093	pobj	XPD,of
R1358	T2095	T2091	acl	differing,forms
R1359	T2096	T2095	advmod	only,differing
R136	T231	T229	pobj	alleles,of
R1360	T2097	T2095	prep	by,differing
R1361	T2098	T2099	amod	single,substitutions
R1362	T2099	T2097	pobj	substitutions,by
R1363	T2100	T2101	compound	amino,acid
R1364	T2101	T2099	compound	acid,substitutions
R1365	T2102	T2077	punct	", ",were
R1366	T2103	T2077	nsubj	we,were
R1367	T2104	T2077	acomp	unable,were
R1368	T2105	T2106	aux	to,ascertain
R1369	T2106	T2104	xcomp	ascertain,unable
R137	T232	T231	compound	Xpd,alleles
R1370	T2107	T2108	det	the,amount
R1371	T2108	T2106	dobj	amount,ascertain
R1372	T2109	T2108	amod	relative,amount
R1373	T2110	T2108	prep	of,amount
R1374	T2111	T2112	compound	XPD,protein
R1375	T2112	T2110	pobj	protein,of
R1376	T2113	T2112	prep	from,protein
R1377	T2114	T2115	det	the,alleles
R1378	T2115	T2113	pobj	alleles,from
R1379	T2116	T2115	amod	different,alleles
R138	T233	T219	punct	", ",variety
R1380	T2117	T2077	punct	.,were
R1381	T2119	T2120	prep	Despite,ameliorated
R1382	T2121	T2122	amod	reduced,levels
R1383	T2122	T2119	pobj	levels,Despite
R1384	T2123	T2122	prep	of,levels
R1385	T2124	T2125	compound	mRNA,expression
R1386	T2125	T2123	pobj	expression,of
R1387	T2126	T2120	punct	", ",ameliorated
R1388	T2127	T2128	det	the,allele
R1389	T2128	T2120	nsubj	allele,ameliorated
R139	T234	T219	prep	including,variety
R1390	T2129	T2128	amod	homozygous,allele
R1391	T2130	T2128	amod	lethal,allele
R1392	T2131	T2128	compound	Xpd†XPCS,allele
R1393	T2132	T2133	amod	multiple,symptoms
R1394	T2133	T2120	dobj	symptoms,ameliorated
R1395	T2134	T2135	npadvmod	XpdTTD,associated
R1396	T2135	T2133	amod	associated,symptoms
R1397	T2136	T2135	punct	-,associated
R1398	T2137	T2133	compound	disease,symptoms
R1399	T2138	T2120	prep	in,ameliorated
R14	T100	T99	punct	", ",heterozygosity
R140	T235	T236	det	the,following
R1400	T2139	T2140	amod	compound,animals
R1401	T2140	T2138	pobj	animals,in
R1402	T2141	T2140	amod	heterozygous,animals
R1403	T2142	T2143	compound	XpdTTD,†XPCS
R1404	T2143	T2140	compound	†XPCS,animals
R1405	T2144	T2143	punct	/,†XPCS
R1406	T2145	T2120	prep	including,ameliorated
R1407	T2146	T2147	det	the,hair
R1408	T2147	T2145	pobj	hair,including
R1409	T2148	T2147	nmod	hallmark,hair
R141	T236	T234	pobj	following,including
R1410	T2149	T2147	amod	brittle,hair
R1411	T2150	T2147	cc	and,hair
R1412	T2151	T2152	amod	cutaneous,features
R1413	T2152	T2147	conj	features,hair
R1414	T2153	T2154	advmod	fully,penetrant
R1415	T2154	T2147	amod	penetrant,hair
R1416	T2155	T2154	prep	in,penetrant
R1417	T2156	T2157	advmod	homo,hemizygous
R1418	T2157	T2160	amod	hemizygous,mice
R1419	T2158	T2157	punct	-,hemizygous
R142	T237	T236	punct	: ,following
R1420	T2159	T2157	cc	and,hemizygous
R1421	T2160	T2155	pobj	mice,in
R1422	T2161	T2160	compound	TTD,mice
R1423	T2162	T2163	punct	(,2A
R1424	T2163	T2120	parataxis	2A,ameliorated
R1425	T2164	T2163	compound	Figure,2A
R1426	T2165	T2166	punct	–,2C
R1427	T2166	T2163	prep	2C,2A
R1428	T2167	T2163	punct	),2A
R1429	T2168	T2120	punct	.,ameliorated
R143	T238	T239	punct	(,i
R1430	T2170	T2171	prep	In,displayed
R1431	T2172	T2173	amod	marked,contrast
R1432	T2173	T2170	pobj	contrast,In
R1433	T2174	T2173	prep	to,contrast
R1434	T2175	T2176	nmod	XpdTTD,TTD
R1435	T2176	T2178	nmod	TTD,mice
R1436	T2177	T2176	punct	/,TTD
R1437	T2178	T2174	pobj	mice,to
R1438	T2179	T2176	punct	(,TTD
R1439	T2180	T2176	cc	and,TTD
R144	T239	T240	meta	i,ability
R1440	T2181	T2182	compound	XpdTTD,KO
R1441	T2182	T2176	conj	KO,TTD
R1442	T2183	T2182	punct	/,KO
R1443	T2184	T2178	punct	),mice
R1444	T2185	T2178	punct	", ",mice
R1445	T2186	T2187	dep	which,display
R1446	T2187	T2178	relcl	display,mice
R1447	T2188	T2189	amod	complete,loss
R1448	T2189	T2187	dobj	loss,display
R1449	T2190	T2189	compound	hair,loss
R145	T240	T236	appos	ability,following
R1450	T2191	T2189	prep	in,loss
R1451	T2192	T2193	det	the,cycle
R1452	T2193	T2191	pobj	cycle,in
R1453	T2194	T2193	amod	first,cycle
R1454	T2195	T2193	compound	hair,cycle
R1455	T2196	T2189	cc	and,loss
R1456	T2197	T2198	amod	partial,loss
R1457	T2198	T2189	conj	loss,loss
R1458	T2199	T2198	compound	hair,loss
R1459	T2200	T2198	prep	in,loss
R146	T241	T239	punct	),i
R1460	T2201	T2202	amod	subsequent,cycles
R1461	T2202	T2200	pobj	cycles,in
R1462	T2203	T2187	prep	throughout,display
R1463	T2204	T2205	poss	their,lives
R1464	T2205	T2203	pobj	lives,throughout
R1465	T2206	T2207	punct	[,21
R1466	T2207	T2187	parataxis	21,display
R1467	T2208	T2207	punct	],21
R1468	T2209	T2171	punct	", ",displayed
R1469	T2210	T2211	nmod	compound,mice
R147	T242	T240	det	the,ability
R1470	T2211	T2171	nsubj	mice,displayed
R1471	T2212	T2211	amod	heterozygous,mice
R1472	T2213	T2211	compound	XpdTTD/†XPCS,mice
R1473	T2214	T2215	det	some,loss
R1474	T2215	T2171	dobj	loss,displayed
R1475	T2216	T2215	compound	hair,loss
R1476	T2217	T2218	advmod	only,during
R1477	T2218	T2171	prep	during,displayed
R1478	T2219	T2220	det	the,cycle
R1479	T2220	T2218	pobj	cycle,during
R148	T243	T240	prep	of,ability
R1480	T2221	T2220	amod	first,cycle
R1481	T2222	T2220	compound	hair,cycle
R1482	T2223	T2218	cc	and,during
R1483	T2224	T2225	advmod	only,locally
R1484	T2225	T2226	advmod	locally,at
R1485	T2226	T2218	conj	at,during
R1486	T2227	T2228	det	the,back
R1487	T2228	T2226	pobj	back,at
R1488	T2229	T2230	punct	(,2A
R1489	T2230	T2171	parataxis	2A,displayed
R149	T244	T245	amod	homozygous,alleles
R1490	T2231	T2230	compound	Figure,2A
R1491	T2232	T2230	punct	),2A
R1492	T2233	T2171	punct	.,displayed
R1493	T2235	T2236	compound	Scanning,microscope
R1494	T2236	T2238	compound	microscope,analysis
R1495	T2237	T2236	compound	electron,microscope
R1496	T2238	T2239	nsubj	analysis,revealed
R1497	T2240	T2238	prep	of,analysis
R1498	T2241	T2242	compound	XpdTTD,†XPCS
R1499	T2242	T2244	compound	†XPCS,hair
R15	T101	T99	cc	or,heterozygosity
R150	T245	T243	pobj	alleles,of
R1500	T2243	T2242	punct	/,†XPCS
R1501	T2244	T2240	pobj	hair,of
R1502	T2245	T2246	det	an,appearance
R1503	T2246	T2239	dobj	appearance,revealed
R1504	T2247	T2248	advmod	almost,normal
R1505	T2248	T2246	amod	normal,appearance
R1506	T2249	T2246	punct	", ",appearance
R1507	T2250	T2246	prep	with,appearance
R1508	T2251	T2252	npadvmod	TTD,like
R1509	T2252	T2254	amod	like,features
R151	T246	T245	amod	lethal,alleles
R1510	T2253	T2252	punct	-,like
R1511	T2254	T2250	pobj	features,with
R1512	T2255	T2256	amod	such,as
R1513	T2256	T2254	prep	as,features
R1514	T2257	T2258	amod	broken,hairs
R1515	T2258	T2256	pobj	hairs,as
R1516	T2259	T2254	acl	found,features
R1517	T2260	T2261	advmod	only,at
R1518	T2261	T2259	prep	at,found
R1519	T2262	T2263	advmod	very,low
R152	T247	T245	compound	Xpd,alleles
R1520	T2263	T2264	amod	low,frequency
R1521	T2264	T2261	pobj	frequency,at
R1522	T2265	T2266	punct	(,data
R1523	T2266	T2239	parataxis	data,revealed
R1524	T2267	T2266	amod	unpublished,data
R1525	T2268	T2266	punct	),data
R1526	T2269	T2239	punct	.,revealed
R1527	T2271	T2272	compound	Amino,acid
R1528	T2272	T2273	compound	acid,analysis
R1529	T2273	T2274	nsubj	analysis,confirmed
R153	T248	T249	aux	to,ameliorate
R1530	T2275	T2276	mark	that,were
R1531	T2276	T2274	ccomp	were,confirmed
R1532	T2277	T2278	compound	cysteine,levels
R1533	T2278	T2276	nsubj	levels,were
R1534	T2279	T2278	prep	in,levels
R1535	T2280	T2281	det	the,hair
R1536	T2281	T2279	pobj	hair,in
R1537	T2282	T2281	prep	of,hair
R1538	T2283	T2284	det	the,mice
R1539	T2284	T2282	pobj	mice,of
R154	T249	T240	acl	ameliorate,ability
R1540	T2285	T2286	compound	XpdTTD,†XPCS
R1541	T2286	T2284	compound	†XPCS,mice
R1542	T2287	T2286	punct	/,†XPCS
R1543	T2288	T2289	advmod	significantly,higher
R1544	T2289	T2276	acomp	higher,were
R1545	T2290	T2289	prep	than,higher
R1546	T2291	T2290	prep	in,than
R1547	T2292	T2293	compound	XpdTTD,TTD
R1548	T2293	T2295	compound	TTD,animals
R1549	T2294	T2293	punct	/,TTD
R155	T250	T251	det	a,variety
R1550	T2295	T2291	pobj	animals,in
R1551	T2296	T2276	punct	", ",were
R1552	T2297	T2276	cc	but,were
R1553	T2298	T2276	conj	remained,were
R1554	T2299	T2298	prep	below,remained
R1555	T2300	T2301	det	the,level
R1556	T2301	T2299	pobj	level,below
R1557	T2302	T2301	compound	wt,level
R1558	T2303	T2304	punct	(,2C
R1559	T2304	T2274	parataxis	2C,confirmed
R156	T251	T249	dobj	variety,ameliorate
R1560	T2305	T2304	compound	Figure,2C
R1561	T2306	T2304	punct	),2C
R1562	T2307	T2274	punct	.,confirmed
R1563	T2309	T2310	compound	TTD,hemizygotes
R1564	T2310	T2311	nsubj	hemizygotes,display
R1565	T2312	T2313	punct	(,KO
R1566	T2313	T2310	parataxis	KO,hemizygotes
R1567	T2314	T2313	compound	XpdTTD,KO
R1568	T2315	T2313	punct	/,KO
R1569	T2316	T2313	punct	),KO
R157	T252	T251	prep	of,variety
R1570	T2317	T2311	aux	do,display
R1571	T2318	T2311	neg	not,display
R1572	T2319	T2320	amod	significant,differences
R1573	T2320	T2311	dobj	differences,display
R1574	T2321	T2320	prep	in,differences
R1575	T2322	T2323	amod	cutaneous,features
R1576	T2323	T2321	pobj	features,in
R1577	T2324	T2323	cc	and,features
R1578	T2325	T2323	conj	longevity,features
R1579	T2326	T2320	amod	relative,differences
R158	T253	T254	compound	disease,symptoms
R1580	T2327	T2326	prep	to,relative
R1581	T2328	T2329	amod	homozygous,mice
R1582	T2329	T2327	pobj	mice,to
R1583	T2330	T2331	compound	XpdTTD,TTD
R1584	T2331	T2329	compound	TTD,mice
R1585	T2332	T2331	punct	/,TTD
R1586	T2333	T2334	punct	[,21
R1587	T2334	T2311	parataxis	21,display
R1588	T2335	T2334	punct	],21
R1589	T2336	T2311	punct	.,display
R159	T254	T252	pobj	symptoms,of
R1590	T2338	T2339	amod	Other,features
R1591	T2339	T2342	nsubj	features,were
R1592	T2340	T2339	amod	prominent,features
R1593	T2341	T2339	compound	TTD,features
R1594	T2343	T2339	prep	in,features
R1595	T2344	T2345	det	the,epidermis
R1596	T2345	T2343	pobj	epidermis,in
R1597	T2346	T2339	punct	", ",features
R1598	T2347	T2339	prep	including,features
R1599	T2348	T2347	pobj	acanthosis,including
R16	T102	T103	det	the,presence
R160	T255	T256	advmod	when,supplied
R1600	T2349	T2350	punct	(,thickening
R1601	T2350	T2348	parataxis	thickening,acanthosis
R1602	T2351	T2350	prep	of,thickening
R1603	T2352	T2353	det	the,layer
R1604	T2353	T2351	pobj	layer,of
R1605	T2354	T2353	prep	of,layer
R1606	T2355	T2356	det	the,cells
R1607	T2356	T2354	pobj	cells,of
R1608	T2357	T2356	amod	nucleated,cells
R1609	T2358	T2350	punct	),thickening
R161	T256	T249	advcl	supplied,ameliorate
R1610	T2359	T2348	punct	", ",acanthosis
R1611	T2360	T2348	conj	hyperkeratosis,acanthosis
R1612	T2361	T2362	punct	(,thickening
R1613	T2362	T2360	parataxis	thickening,hyperkeratosis
R1614	T2363	T2362	amod	prominent,thickening
R1615	T2364	T2362	prep	of,thickening
R1616	T2365	T2366	det	the,layer
R1617	T2366	T2364	pobj	layer,of
R1618	T2367	T2366	amod	cornified,layer
R1619	T2368	T2362	punct	),thickening
R162	T257	T258	poss	their,function
R1620	T2369	T2360	punct	", ",hyperkeratosis
R1621	T2370	T2360	cc	and,hyperkeratosis
R1622	T2371	T2372	amod	pronounced,layer
R1623	T2372	T2360	conj	layer,hyperkeratosis
R1624	T2373	T2372	amod	granular,layer
R1625	T2374	T2372	cc	and,layer
R1626	T2375	T2376	amod	sebacious,gland
R1627	T2376	T2377	compound	gland,hyperplasia
R1628	T2377	T2372	conj	hyperplasia,layer
R1629	T2378	T2379	punct	(,causing
R163	T258	T256	nsubjpass	function,supplied
R1630	T2379	T2377	parataxis	causing,hyperplasia
R1631	T2380	T2381	amod	greasy,appearance
R1632	T2381	T2379	dobj	appearance,causing
R1633	T2382	T2381	prep	of,appearance
R1634	T2383	T2384	det	the,hair
R1635	T2384	T2382	pobj	hair,of
R1636	T2385	T2379	punct	),causing
R1637	T2386	T2342	punct	", ",were
R1638	T2387	T2342	acomp	absent,were
R1639	T2388	T2342	prep	in,were
R164	T259	T258	amod	essential,function
R1640	T2389	T2390	det	the,skin
R1641	T2390	T2388	pobj	skin,in
R1642	T2391	T2390	prep	of,skin
R1643	T2392	T2393	compound	XpdTTD,†XPCS
R1644	T2393	T2395	compound	†XPCS,mice
R1645	T2394	T2393	punct	/,†XPCS
R1646	T2395	T2391	pobj	mice,of
R1647	T2396	T2342	punct	", ",were
R1648	T2397	T2398	mark	as,established
R1649	T2398	T2342	advcl	established,were
R165	T260	T258	amod	basal,function
R1650	T2399	T2398	prep	by,established
R1651	T2400	T2401	amod	blind,examination
R1652	T2401	T2399	pobj	examination,by
R1653	T2402	T2401	amod	microscopic,examination
R1654	T2403	T2401	prep	of,examination
R1655	T2404	T2405	compound	skin,sections
R1656	T2405	T2403	pobj	sections,of
R1657	T2406	T2407	punct	(,2B
R1658	T2407	T2342	parataxis	2B,were
R1659	T2408	T2407	compound	Figure,2B
R166	T261	T258	compound	transcription,function
R1660	T2409	T2407	punct	),2B
R1661	T2410	T2342	punct	.,were
R1662	T2412	T2413	advmod	Furthermore,rescued
R1663	T2414	T2413	punct	", ",rescued
R1664	T2415	T2413	nsubjpass	anaemia,rescued
R1665	T2416	T2415	cc	and,anaemia
R1666	T2417	T2418	amod	developmental,delay
R1667	T2418	T2415	conj	delay,anaemia
R1668	T2419	T2415	amod	present,anaemia
R1669	T2420	T2419	prep	in,present
R167	T262	T256	auxpass	is,supplied
R1670	T2421	T2420	pobj	patients,in
R1671	T2422	T2421	prep	with,patients
R1672	T2423	T2422	pobj	TTD,with
R1673	T2424	T2425	punct	[,24
R1674	T2425	T2421	parataxis	24,patients
R1675	T2426	T2425	punct	],24
R1676	T2427	T2420	cc	and,in
R1677	T2428	T2420	conj	in,in
R1678	T2429	T2430	compound	XpdTTD,TTD
R1679	T2430	T2432	compound	TTD,mice
R168	T263	T256	agent	by,supplied
R1680	T2431	T2430	punct	/,TTD
R1681	T2432	T2428	pobj	mice,in
R1682	T2433	T2434	punct	[,15
R1683	T2434	T2432	parataxis	15,mice
R1684	T2435	T2434	punct	],15
R1685	T2436	T2413	auxpass	were,rescued
R1686	T2437	T2413	advmod	both,rescued
R1687	T2438	T2413	advmod	partially,rescued
R1688	T2439	T2413	prep	in,rescued
R1689	T2440	T2441	amod	compound,mice
R169	T264	T265	det	a,allele
R1690	T2441	T2439	pobj	mice,in
R1691	T2442	T2441	amod	heterozygous,mice
R1692	T2443	T2444	compound	XpdTTD,†XPCS
R1693	T2444	T2441	compound	†XPCS,mice
R1694	T2445	T2444	punct	/,†XPCS
R1695	T2446	T2447	punct	(,2D
R1696	T2447	T2413	parataxis	2D,rescued
R1697	T2448	T2447	compound	Figure,2D
R1698	T2449	T2447	cc	and,2D
R1699	T2450	T2447	conj	2E,2D
R17	T103	T99	conj	presence,heterozygosity
R170	T265	T263	pobj	allele,by
R1700	T2451	T2447	punct	),2D
R1701	T2452	T2413	punct	.,rescued
R1702	T2573	T2572	prep	of,Rescue
R1703	T2574	T2575	amod	"Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles Compound Heterozygosity at theXpd Locus Abstract Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of “null” alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals. Effects of mutations in Xpd were investigated in mice. Compound heterozygotes of otherwise homozygous lethal alleles demonstrated interallelic complementation and partial phenotypic rescue of XPD-related disease symptoms. Introduction Interallelic complementation is defined as the ability of two differentially mutated alleles to function better together than either can on its own. Despite its near universality in lower organisms [1], its potential to contribute to clinical heterogeneity in human disease is seldom considered. Evidence of interallelic complementation at clinically relevant loci is limited to biochemical and cell-based studies of a handful of metabolic disorders with defects in enzymes including propinyl-CoA carboxylase [2], argininosuccinate lyase [3], galactose-1-phosphate uridylyltransferase [4], and methylmalonyl CoA mutase [5]. Compound heterozygotes are individuals carrying two different mutant alleles of the same gene. In the absence of a dominant (wild-type [wt]) allele, genetic interactions between recessive alleles (referred to here as “biallelic” effects) could result in different phenotypic outcomes including interallelic complementation. Although amelioration of disease symptoms by interallelic complementation would create an ascertainment bias in the clinic, the lack of evidence concerning interallelic complementation or other biallelic effects in human disease is likely caused by the difficulty in distinguishing such effects from environment and genetic background. XPD encodes one of the two helicase components of basal transcription/DNA repair factor IIH (TFIIH), a ten-subunit, multifunctional complex that is essential for multiple processes, including basal transcription initiation and DNA damage repair via the nucleotide excision repair (NER) pathway [6,7]. Alterations in XPD resulting in defective TFIIH function are associated with UV-sensitive, multisystem disorders including xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD) [8–10]. XP is marked by sun-induced pigmentation anomalies and a greater than 1,000-fold elevation in skin cancer risk. Severe cases can also present with growth retardation and primary neurodegeneration [11]. CS and TTD, on the other hand, are segmental progeroid disorders characterised by progressive post-natal growth failure and primary demyelination resulting in severe neurodysfunction, but without a clear cancer predisposition [12–15]. Patients with TTD additionally display hallmark sulphur-deficient brittle hair and nails and scaling skin [13], resulting from a basal transcription defect in specific cell types [16,17]. A related disorder with the cancer predisposition of XP combined with the neurodevelopmental complications of CS (XPCS), although rare, has also been described [18]. Many XPD mutations are associated with an exclusive disease phenotype (e.g., XPDR722W with TTD and XPDR683W with XP) and are thus viewed as causative of the corresponding syndromes. Alleles not associated exclusively with one disorder are considered “likely null” alleles [19,20]. Some of these alleles fail to support viability in a haploid Schizosaccharomyces pombe yeast strain with a null mutation in the XPD homologue rad15 and are thus considered devoid of significant biological activity [19]. This classification of alleles as either causative or null currently defines what we refer to as a “monoallelic” paradigm of XPD disease. However, the identification in recent years of XP complementation group D patients with atypical disease presentation, including symptoms of both XP and TTD [8], casts doubt on the ability of such a monoallelic paradigm to explain clinical heterogeneity in compound heterozygotes. Previously, we generated a TTD mouse model (XPDR722W) that phenocopies the human syndrome [15,21]. Here we report the generation of additional mutant Xpd alleles that fail to support viability on their own but nevertheless ameliorate TTD-associated premature segmental ageing, cutaneous features, cellular DNA repair capacity, and UV survival when present in a compound heterozygote state. Results Generation of Xpd Compound Heterozygotes We generated an Xpd knock-in allele with a point mutation encoding a single amino acid change (XPDG602D) found in the XPCS patient XPCS2 (Figure 1A–1C). mRNA expression from the targeted allele could be detected in embryonic stem cells by RT-PCR (Figure 1D), although expression was reduced approximately 5-fold relative to wt mRNA transcript levels as determined by Northern blotting of RNA from the testis of heterozygous animals (Figure 1E). Because patient XPCS2 was a hemizygote with mutant XPD protein (XPDG602D) expressed from a single allele, the corresponding mutation was expected to be viable in the homozygous state. However, homozygous mutant mice were not observed, neither amongst live births nor embryonic day 13.5 (E13.5) or E3.5 embryos (Table 1). The corresponding hypomorphic, mutant allele was thus designated as homozygous lethal (†XPCS). Homozygous lethality of the XPCS allele is likely due to reduced levels of expression of this essential protein as a result of gene targeting (Figure 1A) rather than to the mutation itself. Xpd ablation (XpdKO /KO ) is similarly incompatible with life beyond the earliest stages of embryogenesis [22]. Consistent with this interpretation, a different targeted Xpd mutation encoding XPDR683W, which is associated with XP in the homozygous state in humans, was similarly underexpressed and lethal in the homozygous state (designated as †XP allele) (Figure 1A–1C; Table 1; unpublished data). Also, a different targeting approach leading to the use of the native 3′UTR and removal of the neo gene resulted in normalisation of XpdXPCS mRNA levels and viable homozygous XpdXPCS/XPCS (XPDG602D/G602D) animals [23]. Figure 1 Targeting of the Mouse Xpd Gene (A) Schematic representation of the genomic structure and partial restriction map of the wt and targeted mouse Xpd loci. For the wt Xpd allele, shaded boxes represent coding regions of exons 12 and 19–23; the 3′UTR is represented by an open box. TGA indicates the translational stop codon; PolyA indicates the polyadenylation signal. For the XpdTTD targeted allele, the 194–base pair (bp) human XPD cDNA fragment fused to exon 22 is indicated as a striped box including the TTD (R722W) mutation indicated by a vertical arrow. Chicken β-globin exons 2 and 3 including the 3′UTR are indicated as black boxes with corresponding Roman numerals followed by the β-globin polyadenylation signal (PolyA*). For the Xpd†XP and Xpd†XPCS targeted alleles, vertical arrows indicate XPCS (G602D-encoding) and XP (R683W-encoding) mutations in exons 19 and 22, respectively. The unique 3′ probe located outside the targeting construct is marked by a thick black line. Restriction sites: B, BamHI; C, ClaI; E, EcoRI; H, HindIII; Hp, HpaI; Sf, SfiI. (B) Southern blot analysis of EcoRI-digested genomic DNA from wt, Xpd†XPCS/wt, and Xpd†XP/wt recombinant embryonic stem cell clones hybridised with the 3′ probe depicted in (A). The wt allele yields a 6.5-kilobase (kb) fragment, whereas both targeted Xpd†XP and Xpd†XPCS alleles yield a 5.1-kb fragment. (C) Genotyping of wt and targeted alleles by PCR using primers F2, R1, and mR as indicated in (A) yields fragments of 399 bp and 468 bp, respectively. (D) RT-PCR detection of mRNA expression originating from the targeted †XP and †XPCS alleles in embryonic stem cell clones using primers F1 (hybridising outside the targeting construct) and mR as indicated in (A) results in a 1,416-bp fragment. (E) Northern blot analysis of total RNA isolated from testis of homozygous wt and XpdTTD/TTD, heterozygous Xpd†XPCS/wt and XpdTTD/wt, and compound heterozygous Xpd†XPCS/TTD mice as indicated. Hybridisation with a 1.4-kb mouse Xpd cDNA probe detects mRNAs of 4, 3.3, and 2.7 kb from wt, Xpd†XPCS, and XpdTTD alleles, respectively. An ethidium bromide (EtBr)–stained gel showing the amount of total RNA loaded is shown below. Table 1 Frequency of Xpd†XP/†XP, Xpd†XPCS/†XPCS, and Compound Heterozygous Xpd†XP/†XPCS Embryos and Offspring “Null” Allele Can Alleviate Developmental Delay, Skin, and Hair Features of TTD To test the potential of a homozygous lethal “null” allele to nevertheless contribute to organismal phenotype, we combined an Xpd†XPCS allele with a viable XpdTTD allele by crossing the corresponding heterozygous animals. Similar to hemizygous TTD mice carrying one true Xpd knockout allele (XpdTTD/KO), compound heterozygous XpdTTD/†XPCS mice were born at the expected Mendelian frequencies. Expression from the Xpd†XPCS allele was also reduced in the testis of compound heterozygous animals, whereas expression from the XpdTTD allele was increased relative to wt by ~5-fold (Figure 1E). Because of a lack of available antibodies and the inability to distinguish amongst various mutant forms of XPD differing only by single amino acid substitutions, we were unable to ascertain the relative amount of XPD protein from the different alleles. Despite reduced levels of mRNA expression, the homozygous lethal Xpd†XPCS allele ameliorated multiple XpdTTD-associated disease symptoms in compound heterozygous XpdTTD/†XPCS animals including the hallmark brittle hair and cutaneous features fully penetrant in homo- and hemizygous TTD mice (Figure 2A–2C). In marked contrast to XpdTTD/TTD (and XpdTTD/KO) mice, which display complete hair loss in the first hair cycle and partial hair loss in subsequent cycles throughout their lives [21], compound heterozygous XpdTTD/†XPCS mice displayed some hair loss only during the first hair cycle and only locally at the back (Figure 2A). Scanning electron microscope analysis of XpdTTD/†XPCS hair revealed an almost normal appearance, with TTD-like features such as broken hairs found only at very low frequency (unpublished data). Amino acid analysis confirmed that cysteine levels in the hair of the XpdTTD/†XPCS mice were significantly higher than in XpdTTD/TTD animals, but remained below the wt level (Figure 2C). TTD hemizygotes (XpdTTD/KO) do not display significant differences in cutaneous features and longevity relative to homozygous XpdTTD/TTD mice [21]. Figure 2 Partial Rescue of TTD Cutaneous, Blood, and Developmental Phenotypes in Compound Heterozygous XpdTTD/†XPCS Mice (A) Photographs of 5-mo-old homozygous XpdTTD/TTD, compound heterozygous XpdTTD/†XPCS, and wt mice. Insets: images of first-round hair loss. (B) Histological analysis of the skin of XpdTTD/TTD, XpdTTD/†XPCS, and wt mice. TTD-associated acanthosis (thicker epidermis, indicated by solid vertical line), pronounced granular layer (indicated by arrows), and sebacious gland hyperplasia (indicated by dotted vertical line) were absent in the epidermis of XpdTTD/†XPCS and wt mice. Magnification 400×. (C) Cysteine content of hair from wt, XpdTTD/TTD, and XpdTTD/†XPCS mice. The p-value indicates significant differences between mutants and wt, as well as between XpdTTD/TTD and XpdTTD/†XPCS mice. Error bars indicate standard error of the mean (SEM). (D) Hematocrit values from blood of XpdTTD/TTD and XpdTTD/†XPCS mice. The p-values indicate the significance of the difference relative to wt. Error bars indicate SEM. (E) Body weights of developing XpdTTD/TTD and XpdTTD/†XPCS mice after weaning plotted as a percentage of the weight of age-matched control wt and heterozygote (hz) littermates (set at 100%). Error bars indicate SEM. Other prominent TTD features in the epidermis, including acanthosis (thickening of the layer of the nucleated cells), hyperkeratosis (prominent thickening of the cornified layer), and pronounced granular layer and sebacious gland hyperplasia (causing greasy appearance of the hair), were absent in the skin of XpdTTD/†XPCS mice, as established by blind microscopic examination of skin sections (Figure 2B). Furthermore, anaemia and developmental delay present in patients with TTD [24] and in XpdTTD/TTD mice [15] were both partially rescued in compound heterozygous XpdTTD/†XPCS mice (Figure 2D and 2E). Rescue of Progeroid",Features
R1704	T2575	T2573	pobj	Features,of
R1705	T2576	T2572	prep	in,Rescue
R1706	T2577	T2578	compound	TTD,Mice
R1707	T2578	T2576	pobj	Mice,in
R1708	T2579	T2572	prep	by,Rescue
R1709	T2580	T2581	amod	Homozygous,Alleles
R171	T266	T265	amod	different,allele
R1710	T2581	T2579	pobj	Alleles,by
R1711	T2582	T2581	amod	Lethal,Alleles
R1712	T2583	T2581	compound	Xpd,Alleles
R1713	T2585	T2586	mark	Because,share
R1714	T2586	T2605	advcl	share,addressed
R1715	T2587	T2586	nsubj	patients,share
R1716	T2588	T2587	prep	with,patients
R1717	T2589	T2588	pobj	TTD,with
R1718	T2590	T2589	punct	", ",TTD
R1719	T2591	T2589	conj	XPCS,TTD
R172	T267	T268	npadvmod	disease,causing
R1720	T2592	T2591	punct	", ",XPCS
R1721	T2593	T2591	cc	and,XPCS
R1722	T2594	T2591	conj	CS,XPCS
R1723	T2595	T2589	punct	(,TTD
R1724	T2596	T2589	cc	but,TTD
R1725	T2597	T2596	neg	not,but
R1726	T2598	T2589	conj	XP,TTD
R1727	T2599	T2587	punct	),patients
R1728	T2600	T2587	cc	and,patients
R1729	T2601	T2602	det	the,models
R173	T268	T265	amod	causing,allele
R1730	T2602	T2587	conj	models,patients
R1731	T2603	T2602	amod	corresponding,models
R1732	T2604	T2602	compound	mouse,models
R1733	T2606	T2607	amod	similar,symptoms
R1734	T2607	T2586	dobj	symptoms,share
R1735	T2608	T2607	amod	accelerated,symptoms
R1736	T2609	T2607	compound	progeroid,symptoms
R1737	T2610	T2611	punct	[,23
R1738	T2611	T2586	parataxis	23,share
R1739	T2612	T2611	nummod	12,23
R174	T269	T268	punct	-,causing
R1740	T2613	T2611	punct	",",23
R1741	T2614	T2611	nummod	13,23
R1742	T2615	T2611	punct	",",23
R1743	T2616	T2611	nummod	15,23
R1744	T2617	T2611	punct	",",23
R1745	T2618	T2611	punct	],23
R1746	T2619	T2605	punct	", ",addressed
R1747	T2620	T2605	nsubj	we,addressed
R1748	T2621	T2605	advmod	next,addressed
R1749	T2622	T2623	amod	ageing,related
R175	T270	T240	punct	", ",ability
R1750	T2623	T2625	amod	related,parameters
R1751	T2624	T2623	punct	-,related
R1752	T2625	T2605	dobj	parameters,addressed
R1753	T2626	T2625	prep	in,parameters
R1754	T2627	T2628	amod	compound,mice
R1755	T2628	T2626	pobj	mice,in
R1756	T2629	T2628	amod	heterozygous,mice
R1757	T2630	T2631	punct	(,Figure
R1758	T2631	T2605	parataxis	Figure,addressed
R1759	T2632	T2631	nummod	3,Figure
R176	T271	T272	punct	(,ii
R1760	T2633	T2631	punct	),Figure
R1761	T2634	T2605	punct	.,addressed
R1762	T2636	T2637	mark	Whereas,show
R1763	T2637	T2642	advcl	show,were
R1764	T2638	T2639	compound	XpdTTD,TTD
R1765	T2639	T2641	compound	TTD,animals
R1766	T2640	T2639	punct	/,TTD
R1767	T2641	T2637	nsubj	animals,show
R1768	T2643	T2644	amod	reduced,density
R1769	T2644	T2637	dobj	density,show
R177	T272	T273	meta	ii,functions
R1770	T2645	T2646	compound	bone,mineral
R1771	T2646	T2644	compound	mineral,density
R1772	T2647	T2637	prep	as,show
R1773	T2648	T2649	det	an,indication
R1774	T2649	T2647	pobj	indication,as
R1775	T2650	T2649	prep	of,indication
R1776	T2651	T2652	det	the,onset
R1777	T2652	T2650	pobj	onset,of
R1778	T2653	T2652	amod	early,onset
R1779	T2654	T2652	prep	of,onset
R178	T273	T240	conj	functions,ability
R1780	T2655	T2654	pobj	osteoporosis,of
R1781	T2656	T2652	prep	before,onset
R1782	T2657	T2658	punct	~,14
R1783	T2658	T2659	nummod	14,mo
R1784	T2659	T2656	pobj	mo,before
R1785	T2660	T2659	prep	of,mo
R1786	T2661	T2660	pobj	age,of
R1787	T2662	T2663	punct	[,15
R1788	T2663	T2637	parataxis	15,show
R1789	T2664	T2663	punct	],15
R179	T274	T272	punct	),ii
R1790	T2665	T2642	punct	", ",were
R1791	T2666	T2667	compound	tail,vertebrae
R1792	T2667	T2642	nsubj	vertebrae,were
R1793	T2668	T2667	prep	from,vertebrae
R1794	T2669	T2670	nmod	compound,mice
R1795	T2670	T2668	pobj	mice,from
R1796	T2671	T2670	amod	heterozygous,mice
R1797	T2672	T2673	compound	XpdTTD,†XPCS
R1798	T2673	T2670	compound	†XPCS,mice
R1799	T2674	T2673	punct	/,†XPCS
R18	T104	T103	prep	of,presence
R180	T275	T276	amod	differential,developmental
R1800	T2675	T2642	acomp	comparable,were
R1801	T2676	T2675	prep	to,comparable
R1802	T2677	T2676	pobj	wt,to
R1803	T2678	T2679	advmod	even,at
R1804	T2679	T2642	prep	at,were
R1805	T2680	T2681	nummod	20,mo
R1806	T2681	T2679	pobj	mo,at
R1807	T2682	T2681	prep	of,mo
R1808	T2683	T2682	pobj	age,of
R1809	T2684	T2685	punct	(,3B
R181	T276	T273	amod	developmental,functions
R1810	T2685	T2642	parataxis	3B,were
R1811	T2686	T2685	compound	Figure,3B
R1812	T2687	T2685	cc	and,3B
R1813	T2688	T2685	conj	3C,3B
R1814	T2689	T2685	punct	),3B
R1815	T2690	T2642	punct	.,were
R1816	T2692	T2693	advmod	Furthermore,3B
R1817	T2694	T2693	punct	", ",3B
R1818	T2695	T2696	mark	whereas,developed
R1819	T2696	T2693	advcl	developed,3B
R182	T277	T276	cc	and,developmental
R1820	T2697	T2698	compound	XpdTTD,TTD
R1821	T2698	T2700	compound	TTD,mice
R1822	T2699	T2698	punct	/,TTD
R1823	T2700	T2696	nsubj	mice,developed
R1824	T2701	T2696	dobj	kyphosis,developed
R1825	T2702	T2696	advmod	earlier,developed
R1826	T2703	T2702	prep	than,earlier
R1827	T2704	T2705	compound	wt,animals
R1828	T2705	T2703	pobj	animals,than
R1829	T2706	T2707	punct	(,onset
R183	T278	T279	npadvmod	tissue,specific
R1830	T2707	T2702	parataxis	onset,earlier
R1831	T2708	T2709	punct	~,3
R1832	T2709	T2710	nummod	3,mo
R1833	T2710	T2707	npadvmod	mo,onset
R1834	T2711	T2710	cc	versus,mo
R1835	T2712	T2713	quantmod	12,20
R1836	T2713	T2715	nummod	20,mo
R1837	T2714	T2713	punct	–,20
R1838	T2715	T2710	conj	mo,mo
R1839	T2716	T2707	punct	),onset
R184	T279	T276	conj	specific,developmental
R1840	T2717	T2693	punct	", ",3B
R1841	T2718	T2719	amod	compound,mice
R1842	T2719	T2693	nsubj	mice,3B
R1843	T2720	T2719	amod	heterozygous,mice
R1844	T2721	T2722	compound	XpdTTD,†XPCS
R1845	T2722	T2719	compound	†XPCS,mice
R1846	T2723	T2722	punct	/,†XPCS
R1847	T2724	T2693	aux	did,3B
R1848	T2725	T2693	neg	not,3B
R1849	T2726	T2693	punct	(,3B
R185	T280	T279	punct	-,specific
R1850	T2727	T2693	compound	Figure,3B
R1851	T2728	T2693	punct	),3B
R1852	T2729	T2693	punct	.,3B
R1853	T2731	T2732	amod	Overall,appearance
R1854	T2732	T2733	nsubj	appearance,revealed
R1855	T2734	T2732	cc	and,appearance
R1856	T2735	T2736	compound	body,weight
R1857	T2736	T2737	compound	weight,curves
R1858	T2737	T2732	conj	curves,appearance
R1859	T2738	T2739	mark	that,rescued
R186	T281	T273	prep	of,functions
R1860	T2739	T2733	ccomp	rescued,revealed
R1861	T2740	T2741	npadvmod	TTD,associated
R1862	T2741	T2743	amod	associated,cachexia
R1863	T2742	T2741	punct	-,associated
R1864	T2743	T2739	nsubjpass	cachexia,rescued
R1865	T2744	T2745	npadvmod	age,related
R1866	T2745	T2743	amod	related,cachexia
R1867	T2746	T2745	punct	-,related
R1868	T2747	T2743	amod	premature,cachexia
R1869	T2748	T2743	cc	and,cachexia
R187	T282	T283	amod	distinct,products
R1870	T2749	T2743	conj	lack,cachexia
R1871	T2750	T2749	prep	of,lack
R1872	T2751	T2752	amod	general,fitness
R1873	T2752	T2750	pobj	fitness,of
R1874	T2753	T2739	auxpass	were,rescued
R1875	T2754	T2739	advmod	fully,rescued
R1876	T2755	T2739	prep	in,rescued
R1877	T2756	T2757	amod	compound,mice
R1878	T2757	T2755	pobj	mice,in
R1879	T2758	T2757	amod	heterozygous,mice
R188	T283	T281	pobj	products,of
R1880	T2759	T2760	compound	XpdTTD,†XPCS
R1881	T2760	T2757	compound	†XPCS,mice
R1882	T2761	T2760	punct	/,†XPCS
R1883	T2762	T2763	punct	(,3A
R1884	T2763	T2733	parataxis	3A,revealed
R1885	T2764	T2763	compound	Figure,3A
R1886	T2765	T2763	cc	and,3A
R1887	T2766	T2763	conj	3D,3A
R1888	T2767	T2763	punct	),3A
R1889	T2768	T2733	punct	.,revealed
R189	T284	T285	compound	Xpd,allele
R1890	T2770	T2771	advmod	Finally,extended
R1891	T2772	T2771	punct	", ",extended
R1892	T2773	T2774	det	the,span
R1893	T2774	T2771	nsubjpass	span,extended
R1894	T2775	T2774	compound	life,span
R1895	T2776	T2774	prep	of,span
R1896	T2777	T2778	amod	compound,heterozygotes
R1897	T2778	T2776	pobj	heterozygotes,of
R1898	T2779	T2771	auxpass	was,extended
R1899	T2780	T2771	advcl	relative,extended
R19	T105	T106	nummod	two,alleles
R190	T285	T283	compound	allele,products
R1900	T2781	T2780	prep	to,relative
R1901	T2782	T2783	compound	XpdTTD,TTD
R1902	T2783	T2785	compound	TTD,mice
R1903	T2784	T2783	punct	/,TTD
R1904	T2785	T2781	pobj	mice,to
R1905	T2786	T2787	punct	(,Table
R1906	T2787	T2771	parataxis	Table,extended
R1907	T2788	T2787	nummod	2,Table
R1908	T2789	T2787	punct	),Table
R1909	T2790	T2771	punct	.,extended
R191	T286	T273	punct	", ",functions
R1910	T2792	T2793	aux	To,determine
R1911	T2793	T2794	advcl	determine,generated
R1912	T2795	T2796	mark	whether,was
R1913	T2796	T2793	ccomp	was,determine
R1914	T2797	T2798	det	the,allele
R1915	T2798	T2796	nsubj	allele,was
R1916	T2799	T2798	amod	homozygous,allele
R1917	T2800	T2798	amod	lethal,allele
R1918	T2801	T2798	compound	Xpd†XPCS,allele
R1919	T2802	T2796	acomp	unique,was
R192	T287	T273	cc	and,functions
R1920	T2803	T2802	prep	in,unique
R1921	T2804	T2805	poss	its,ability
R1922	T2805	T2803	pobj	ability,in
R1923	T2806	T2807	aux	to,ameliorate
R1924	T2807	T2805	acl	ameliorate,ability
R1925	T2808	T2807	dobj	symptoms,ameliorate
R1926	T2809	T2808	acl	associated,symptoms
R1927	T2810	T2809	prep	with,associated
R1928	T2811	T2812	det	the,allele
R1929	T2812	T2810	pobj	allele,with
R193	T288	T289	punct	(,iii
R1930	T2813	T2812	compound	XpdTTD,allele
R1931	T2814	T2794	punct	", ",generated
R1932	T2815	T2794	nsubj	we,generated
R1933	T2816	T2817	nmod	compound,mice
R1934	T2817	T2794	dobj	mice,generated
R1935	T2818	T2817	amod	heterozygous,mice
R1936	T2819	T2820	compound	XpdTTD,†XP
R1937	T2820	T2817	compound	†XP,mice
R1938	T2821	T2820	punct	/,†XP
R1939	T2822	T2794	prep	by,generated
R194	T289	T290	meta	iii,complementation
R1940	T2823	T2822	pcomp	crossing,by
R1941	T2824	T2825	det	the,animals
R1942	T2825	T2823	dobj	animals,crossing
R1943	T2826	T2825	amod	corresponding,animals
R1944	T2827	T2825	amod	heterozygous,animals
R1945	T2828	T2794	punct	.,generated
R1946	T2830	T2831	advcl	Similar,rescued
R1947	T2832	T2830	prep	to,Similar
R1948	T2833	T2834	det	the,allele
R1949	T2834	T2832	pobj	allele,to
R195	T290	T273	conj	complementation,functions
R1950	T2835	T2834	compound	Xpd †XPCS,allele
R1951	T2836	T2831	punct	", ",rescued
R1952	T2837	T2838	det	the,allele
R1953	T2838	T2831	nsubj	allele,rescued
R1954	T2839	T2838	amod	homozygous,allele
R1955	T2840	T2838	amod	lethal,allele
R1956	T2841	T2838	compound	Xpd †XP,allele
R1957	T2842	T2843	amod	cutaneous,symptoms
R1958	T2843	T2831	dobj	symptoms,rescued
R1959	T2844	T2843	prep	including,symptoms
R196	T291	T289	punct	),iii
R1960	T2845	T2846	compound	hair,loss
R1961	T2846	T2844	pobj	loss,including
R1962	T2847	T2848	punct	(,data
R1963	T2848	T2846	parataxis	data,loss
R1964	T2849	T2848	prep	except,data
R1965	T2850	T2849	pcomp	locally,except
R1966	T2851	T2850	prep	during,locally
R1967	T2852	T2853	det	the,round
R1968	T2853	T2851	pobj	round,during
R1969	T2854	T2853	amod	first,round
R197	T292	T290	amod	interallelic,complementation
R1970	T2855	T2848	punct	;,data
R1971	T2856	T2848	amod	unpublished,data
R1972	T2857	T2848	punct	),data
R1973	T2858	T2846	punct	", ",loss
R1974	T2859	T2860	amod	reduced,content
R1975	T2860	T2846	conj	content,loss
R1976	T2861	T2860	compound	cysteine,content
R1977	T2862	T2863	punct	(,index
R1978	T2863	T2860	parataxis	index,content
R1979	T2864	T2863	compound	cysteine,index
R198	T293	T290	punct	", ",complementation
R1980	T2865	T2863	npadvmod	9.3,index
R1981	T2866	T2865	punct	±,9.3
R1982	T2867	T2868	nummod	0.9,deviation
R1983	T2868	T2865	appos	deviation,9.3
R1984	T2869	T2868	amod	standard,deviation
R1985	T2870	T2871	punct	[,%
R1986	T2871	T2865	parataxis	%,9.3
R1987	T2872	T2871	nummod	87,%
R1988	T2873	T2871	prep	of,%
R1989	T2874	T2873	pobj	wt,of
R199	T294	T295	det	a,phenomenon
R1990	T2875	T2871	punct	],%
R1991	T2876	T2863	punct	", ",index
R1992	T2877	T2878	nsubj	p,TTD
R1993	T2878	T2863	ccomp	TTD,index
R1994	T2879	T2878	punct	=,TTD
R1995	T2880	T2878	nummod	0.01,TTD
R1996	T2881	T2878	cc	versus,TTD
R1997	T2882	T2863	punct	),index
R1998	T2883	T2860	punct	", ",content
R1999	T2884	T2885	npadvmod	ageing,associated
R2	T87	T86	pobj	Progeria,of
R20	T106	T104	pobj	alleles,of
R200	T295	T290	appos	phenomenon,complementation
R2000	T2885	T2887	amod	associated,cachexia
R2001	T2886	T2885	punct	-,associated
R2002	T2887	T2860	conj	cachexia,content
R2003	T2888	T2887	amod	premature,cachexia
R2004	T2889	T2890	punct	(,were
R2005	T2890	T2887	parataxis	were,cachexia
R2006	T2891	T2890	nsubj	males,were
R2007	T2892	T2891	cc	and,males
R2008	T2893	T2891	conj	females,males
R2009	T2894	T2895	nummod	36.1,6.4
R201	T296	T297	advmod	rarely,reported
R2010	T2895	T2897	nummod	6.4,g
R2011	T2896	T2895	punct	±,6.4
R2012	T2897	T2890	attr	g,were
R2013	T2898	T2899	punct	[,%
R2014	T2899	T2897	parataxis	%,g
R2015	T2900	T2899	nummod	93,%
R2016	T2901	T2899	prep	of,%
R2017	T2902	T2901	pobj	wt,of
R2018	T2903	T2899	punct	],%
R2019	T2904	T2897	cc	and,g
R202	T297	T295	acl	reported,phenomenon
R2020	T2905	T2906	nummod	39.2,3.2
R2021	T2906	T2908	nummod	3.2,g
R2022	T2907	T2906	punct	±,3.2
R2023	T2908	T2897	conj	g,g
R2024	T2909	T2910	punct	[,%
R2025	T2910	T2908	parataxis	%,g
R2026	T2911	T2910	nummod	116,%
R2027	T2912	T2910	prep	of,%
R2028	T2913	T2912	pobj	wt,of
R2029	T2914	T2910	punct	],%
R203	T298	T297	prep	at,reported
R2030	T2915	T2890	punct	", ",were
R2031	T2916	T2890	advmod	respectively,were
R2032	T2917	T2890	punct	),were
R2033	T2918	T2887	punct	", ",cachexia
R2034	T2919	T2887	cc	and,cachexia
R2035	T2920	T2921	amod	reduced,span
R2036	T2921	T2887	conj	span,cachexia
R2037	T2922	T2921	compound	life,span
R2038	T2923	T2924	punct	(,Table
R2039	T2924	T2831	parataxis	Table,rescued
R204	T299	T300	advmod	clinically,relevant
R2040	T2925	T2924	nummod	2,Table
R2041	T2926	T2924	punct	),Table
R2042	T2927	T2831	punct	.,rescued
R2043	T2929	T2930	advcl	Taken,indicate
R2044	T2931	T2929	advmod	together,Taken
R2045	T2932	T2930	punct	", ",indicate
R2046	T2933	T2934	det	these,data
R2047	T2934	T2930	nsubj	data,indicate
R2048	T2935	T2936	mark	that,were
R2049	T2936	T2930	ccomp	were,indicate
R205	T300	T301	amod	relevant,loci
R2050	T2937	T2938	nummod	two,alleles
R2051	T2938	T2936	nsubj	alleles,were
R2052	T2939	T2938	amod	independent,alleles
R2053	T2940	T2938	punct	", ",alleles
R2054	T2941	T2942	dep	which,are
R2055	T2942	T2938	relcl	are,alleles
R2056	T2943	T2942	prep	on,are
R2057	T2944	T2945	poss	their,own
R2058	T2945	T2943	pobj	own,on
R2059	T2946	T2942	acomp	unable,are
R206	T301	T298	pobj	loci,at
R2060	T2947	T2948	aux	to,support
R2061	T2948	T2946	xcomp	support,unable
R2062	T2949	T2948	dobj	viability,support
R2063	T2950	T2951	punct	(,Table
R2064	T2951	T2948	parataxis	Table,support
R2065	T2952	T2951	nummod	1,Table
R2066	T2953	T2951	punct	),Table
R2067	T2954	T2936	punct	", ",were
R2068	T2955	T2936	advmod	nonetheless,were
R2069	T2956	T2936	acomp	able,were
R207	T302	T301	prep	in,loci
R2070	T2957	T2958	aux	to,ameliorate
R2071	T2958	T2956	xcomp	ameliorate,able
R2072	T2959	T2960	npadvmod	TTD,associated
R2073	T2960	T2962	amod	associated,phenotypes
R2074	T2961	T2960	punct	-,associated
R2075	T2962	T2958	dobj	phenotypes,ameliorate
R2076	T2963	T2964	advmod	in,vivo
R2077	T2964	T2958	advmod	vivo,ameliorate
R2078	T2965	T2966	punct	(,Table
R2079	T2966	T2958	parataxis	Table,ameliorate
R208	T303	T302	pobj	mammals,in
R2080	T2967	T2966	nummod	2,Table
R2081	T2968	T2966	punct	),Table
R2082	T2969	T2930	punct	.,indicate
R2083	T3312	T3313	amod	Molecular,Mechanisms
R2084	T3314	T3313	prep	of,Mechanisms
R2085	T3315	T3316	amod	Biallelic,Effects
R2086	T3316	T3314	pobj	Effects,of
R2087	T3318	T3319	nsubj	We,turned
R2088	T3320	T3319	advmod	next,turned
R2089	T3321	T3319	prep	to,turned
R209	T304	T217	punct	.,report
R2090	T3322	T3323	npadvmod	UV,based
R2091	T3323	T3325	amod	based,assays
R2092	T3324	T3323	punct	-,based
R2093	T3325	T3321	pobj	assays,to
R2094	T3326	T3325	amod	cellular,assays
R2095	T3327	T3325	prep	including,assays
R2096	T3328	T3329	amod	unscheduled,synthesis
R2097	T3329	T3327	pobj	synthesis,including
R2098	T3330	T3329	compound	DNA,synthesis
R2099	T3331	T3329	prep	after,synthesis
R21	T107	T106	amod	different,alleles
R210	T306	T307	poss	Our,data
R2100	T3332	T3333	compound	UV,irradiation
R2101	T3333	T3331	pobj	irradiation,after
R2102	T3334	T3335	punct	(,UDS
R2103	T3335	T3329	parataxis	UDS,synthesis
R2104	T3336	T3335	compound	UV,UDS
R2105	T3337	T3335	punct	-,UDS
R2106	T3338	T3335	punct	),UDS
R2107	T3339	T3329	punct	", ",synthesis
R2108	T3340	T3329	conj	recovery,synthesis
R2109	T3341	T3340	prep	of,recovery
R211	T307	T308	nsubj	data,suggest
R2110	T3342	T3343	compound	RNA,synthesis
R2111	T3343	T3341	pobj	synthesis,of
R2112	T3344	T3340	prep	after,recovery
R2113	T3345	T3346	compound	UV,irradiation
R2114	T3346	T3344	pobj	irradiation,after
R2115	T3347	T3348	punct	(,RRS
R2116	T3348	T3340	parataxis	RRS,recovery
R2117	T3349	T3348	compound	UV,RRS
R2118	T3350	T3348	punct	-,RRS
R2119	T3351	T3348	punct	),RRS
R212	T309	T310	det	a,re-evaluation
R2120	T3352	T3340	punct	", ",recovery
R2121	T3353	T3340	cc	and,recovery
R2122	T3354	T3355	compound	UV,survival
R2123	T3355	T3340	conj	survival,recovery
R2124	T3356	T3329	punct	", ",synthesis
R2125	T3357	T3358	dep	which,report
R2126	T3358	T3329	relcl	report,synthesis
R2127	T3359	T3358	prep	on,report
R2128	T3360	T3361	det	the,subpathways
R2129	T3361	T3359	pobj	subpathways,on
R213	T310	T308	dobj	re-evaluation,suggest
R2130	T3362	T3361	compound	NER,subpathways
R2131	T3363	T3364	punct	(,NER
R2132	T3364	T3361	parataxis	NER,subpathways
R2133	T3365	T3364	amod	global,NER
R2134	T3366	T3364	compound	genome,NER
R2135	T3367	T3364	cc	and,NER
R2136	T3368	T3369	npadvmod	transcription,coupled
R2137	T3369	T3371	amod	coupled,NER
R2138	T3370	T3369	punct	-,coupled
R2139	T3371	T3364	conj	NER,NER
R214	T311	T310	prep	of,re-evaluation
R2140	T3372	T3364	punct	),NER
R2141	T3373	T3361	cc	and,subpathways
R2142	T3374	T3375	amod	total,NER
R2143	T3375	T3361	conj	NER,subpathways
R2144	T3376	T3358	punct	", ",report
R2145	T3377	T3358	advmod	respectively,report
R2146	T3378	T3319	punct	.,turned
R2147	T3380	T3381	prep	In,improved
R2148	T3382	T3380	pobj	none,In
R2149	T3383	T3382	prep	of,none
R215	T312	T313	det	the,contribution
R2150	T3384	T3385	det	these,assays
R2151	T3385	T3383	pobj	assays,of
R2152	T3386	T3381	auxpass	was,improved
R2153	T3387	T3388	det	the,response
R2154	T3388	T3381	nsubjpass	response,improved
R2155	T3389	T3388	prep	to,response
R2156	T3390	T3389	pobj	UV,to
R2157	T3391	T3381	prep	in,improved
R2158	T3392	T3393	compound	compound,heterozygotes
R2159	T3393	T3391	pobj	heterozygotes,in
R216	T313	T311	pobj	contribution,of
R2160	T3394	T3381	advcl	relative,improved
R2161	T3395	T3394	prep	to,relative
R2162	T3396	T3397	compound	TTD,homozygotes
R2163	T3397	T3395	pobj	homozygotes,to
R2164	T3398	T3399	punct	(,4A
R2165	T3399	T3381	parataxis	4A,improved
R2166	T3400	T3399	compound	Figure,4A
R2167	T3401	T3402	punct	–,4C
R2168	T3402	T3399	prep	4C,4A
R2169	T3403	T3399	punct	),4A
R217	T314	T313	prep	of,contribution
R2170	T3404	T3381	punct	.,improved
R2171	T3406	T3407	advmod	However,observed
R2172	T3408	T3407	punct	", ",observed
R2173	T3409	T3407	prep	unlike,observed
R2174	T3410	T3411	det	the,phenotypes
R2175	T3411	T3409	pobj	phenotypes,unlike
R2176	T3412	T3413	advmod	in,vivo
R2177	T3413	T3411	amod	vivo,phenotypes
R2178	T3414	T3411	compound	TTD,phenotypes
R2179	T3415	T3411	acl	described,phenotypes
R218	T315	T314	punct	“,of
R2180	T3416	T3415	advmod	above,described
R2181	T3417	T3411	punct	", ",phenotypes
R2182	T3418	T3419	prep	in,were
R2183	T3419	T3411	relcl	were,phenotypes
R2184	T3420	T3418	pobj	which,in
R2185	T3421	T3422	nmod	XpdTTD,TTD
R2186	T3422	T3424	nmod	TTD,animals
R2187	T3423	T3422	punct	/,TTD
R2188	T3424	T3419	nsubj	animals,were
R2189	T3425	T3422	cc	and,TTD
R219	T316	T317	amod	null,alleles
R2190	T3426	T3427	compound	XpdTTD,KO
R2191	T3427	T3422	conj	KO,TTD
R2192	T3428	T3427	punct	/,KO
R2193	T3429	T3419	acomp	indistinguishable,were
R2194	T3430	T3407	punct	", ",observed
R2195	T3431	T3432	compound	XpdTTD,effects
R2196	T3432	T3407	nsubjpass	effects,observed
R2197	T3433	T3432	compound	dosage,effects
R2198	T3434	T3407	auxpass	were,observed
R2199	T3435	T3407	prep	in,observed
R22	T108	T106	amod	mutant,alleles
R220	T317	T314	pobj	alleles,of
R2200	T3436	T3437	compound	UV,survival
R2201	T3437	T3435	pobj	survival,in
R2202	T3438	T3437	punct	", ",survival
R2203	T3439	T3440	compound	UV,UDS
R2204	T3440	T3437	conj	UDS,survival
R2205	T3441	T3440	punct	-,UDS
R2206	T3442	T3440	punct	", ",UDS
R2207	T3443	T3440	cc	and,UDS
R2208	T3444	T3445	compound	UV,RRS
R2209	T3445	T3440	conj	RRS,UDS
R221	T318	T317	punct	”,alleles
R2210	T3446	T3445	punct	-,RRS
R2211	T3447	T3407	punct	", ",observed
R2212	T3448	T3407	advcl	indicating,observed
R2213	T3449	T3450	mark	that,correlate
R2214	T3450	T3448	ccomp	correlate,indicating
R2215	T3451	T3452	amod	cellular,parameters
R2216	T3452	T3450	nsubj	parameters,correlate
R2217	T3453	T3454	mark	as,measured
R2218	T3454	T3452	advcl	measured,parameters
R2219	T3455	T3454	prep	in,measured
R222	T319	T313	prep	to,contribution
R2220	T3456	T3455	pobj	fibroblasts,in
R2221	T3457	T3454	advmod	here,measured
R2222	T3458	T3450	aux	do,correlate
R2223	T3459	T3450	neg	not,correlate
R2224	T3460	T3450	advmod	always,correlate
R2225	T3461	T3450	prep	with,correlate
R2226	T3462	T3463	det	the,phenotype
R2227	T3463	T3461	pobj	phenotype,with
R2228	T3464	T3450	prep	at,correlate
R2229	T3465	T3466	det	the,level
R223	T320	T321	compound	XPD,disorders
R2230	T3466	T3464	pobj	level,at
R2231	T3467	T3466	prep	of,level
R2232	T3468	T3469	det	the,organism
R2233	T3469	T3467	pobj	organism,of
R2234	T3470	T3469	amod	intact,organism
R2235	T3471	T3407	punct	.,observed
R2236	T3473	T3474	nmod	XpdTTD,KO
R2237	T3474	T3476	nmod	KO,cells
R2238	T3475	T3474	punct	/,KO
R2239	T3476	T3478	nsubjpass	cells,used
R224	T321	T319	pobj	disorders,to
R2240	T3477	T3476	amod	hemizygous,cells
R2241	T3479	T3478	auxpass	were,used
R2242	T3480	T3478	advmod	thus,used
R2243	T3481	T3478	prep	as,used
R2244	T3482	T3483	det	the,baseline
R2245	T3483	T3481	pobj	baseline,as
R2246	T3484	T3485	prep	on,compare
R2247	T3485	T3483	relcl	compare,baseline
R2248	T3486	T3484	pobj	which,on
R2249	T3487	T3485	aux	to,compare
R225	T322	T308	cc	and,suggest
R2250	T3488	T3489	det	the,activity
R2251	T3489	T3485	dobj	activity,compare
R2252	T3490	T3489	prep	of,activity
R2253	T3491	T3492	nmod	compound,cells
R2254	T3492	T3490	pobj	cells,of
R2255	T3493	T3492	amod	heterozygous,cells
R2256	T3494	T3478	punct	.,used
R2257	T3496	T3497	advcl	Relative,improved
R2258	T3498	T3496	prep	to,Relative
R2259	T3499	T3500	compound	XpdTTD,KO
R226	T323	T308	conj	highlight,suggest
R2260	T3500	T3502	compound	KO,cells
R2261	T3501	T3500	punct	/,KO
R2262	T3502	T3498	pobj	cells,to
R2263	T3503	T3502	compound	hemizygote,cells
R2264	T3504	T3497	punct	", ",improved
R2265	T3505	T3506	compound	UV,survival
R2266	T3506	T3497	nsubjpass	survival,improved
R2267	T3507	T3497	auxpass	was,improved
R2268	T3508	T3497	prep	by,improved
R2269	T3509	T3510	det	the,allele
R227	T324	T325	det	the,potential
R2270	T3510	T3508	pobj	allele,by
R2271	T3511	T3510	amod	homozygous,allele
R2272	T3512	T3510	amod	lethal,allele
R2273	T3513	T3510	compound	Xpd†XPCS,allele
R2274	T3514	T3510	prep	in,allele
R2275	T3515	T3516	nmod	XpdTTD,†XPCS
R2276	T3516	T3518	nmod	†XPCS,cells
R2277	T3517	T3516	punct	/,†XPCS
R2278	T3518	T3514	pobj	cells,in
R2279	T3519	T3518	nmod	compound,cells
R228	T325	T323	dobj	potential,highlight
R2280	T3520	T3518	amod	heterozygous,cells
R2281	T3521	T3508	cc	and,by
R2282	T3522	T3523	prep	to,by
R2283	T3523	T3508	conj	by,by
R2284	T3524	T3525	det	a,degree
R2285	T3525	T3522	pobj	degree,to
R2286	T3526	T3525	amod	lesser,degree
R2287	T3527	T3528	det	the,allele
R2288	T3528	T3523	pobj	allele,by
R2289	T3529	T3528	compound	Xpd†XP,allele
R229	T326	T325	prep	of,potential
R2290	T3530	T3531	punct	(,4A
R2291	T3531	T3497	parataxis	4A,improved
R2292	T3532	T3531	compound	Figure,4A
R2293	T3533	T3531	punct	),4A
R2294	T3534	T3497	punct	.,improved
R2295	T3536	T3537	prep	Because,were
R2296	T3538	T3536	pcomp	of,Because
R2297	T3539	T3540	amod	embryonic,lethality
R2298	T3540	T3536	pobj	lethality,Because
R2299	T3541	T3539	cc	and,embryonic
R23	T109	T106	prep	of,alleles
R230	T327	T326	pobj	combinations,of
R2300	T3542	T3539	conj	cellular,embryonic
R2301	T3543	T3537	punct	", ",were
R2302	T3544	T3537	nsubj	we,were
R2303	T3545	T3537	acomp	unable,were
R2304	T3546	T3547	aux	to,test
R2305	T3547	T3545	xcomp	test,unable
R2306	T3548	T3549	compound	UV,survival
R2307	T3549	T3547	dobj	survival,test
R2308	T3550	T3549	acl	associated,survival
R2309	T3551	T3550	advmod	exclusively,associated
R231	T328	T327	prep	of,combinations
R2310	T3552	T3550	prep	with,associated
R2311	T3553	T3554	det	the,alleles
R2312	T3554	T3552	pobj	alleles,with
R2313	T3555	T3554	nmod	Xpd†XPCS,alleles
R2314	T3556	T3555	cc	or,Xpd†XPCS
R2315	T3557	T3555	conj	Xpd†XP,Xpd†XPCS
R2316	T3558	T3537	punct	.,were
R2317	T3560	T3561	advmod	However,known
R2318	T3562	T3561	punct	", ",known
R2319	T3563	T3564	amod	homozygous,XPDXP
R232	T329	T330	amod	recessive,alleles
R2320	T3564	T3565	nmod	XPDXP,cells
R2321	T3565	T3561	nsubjpass	cells,known
R2322	T3566	T3567	punct	(,XPDR683W
R2323	T3567	T3564	parataxis	XPDR683W,XPDXP
R2324	T3568	T3567	punct	),XPDR683W
R2325	T3569	T3564	cc	and,XPDXP
R2326	T3570	T3571	amod	hemizygous,XPDXPCS
R2327	T3571	T3564	conj	XPDXPCS,XPDXP
R2328	T3572	T3573	punct	(,XPDG602D
R2329	T3573	T3571	parataxis	XPDG602D,XPDXPCS
R233	T330	T328	pobj	alleles,of
R2330	T3574	T3573	punct	),XPDG602D
R2331	T3575	T3565	amod	human,cells
R2332	T3576	T3561	auxpass	are,known
R2333	T3577	T3578	aux	to,be
R2334	T3578	T3561	xcomp	be,known
R2335	T3579	T3580	advmod	highly,sensitive
R2336	T3580	T3578	acomp	sensitive,be
R2337	T3581	T3580	prep	to,sensitive
R2338	T3582	T3581	pobj	UV,to
R2339	T3583	T3584	punct	[,25
R234	T331	T332	aux	to,affect
R2340	T3584	T3578	parataxis	25,be
R2341	T3585	T3584	nummod	19,25
R2342	T3586	T3584	punct	",",25
R2343	T3587	T3584	punct	],25
R2344	T3588	T3561	punct	", ",known
R2345	T3589	T3590	mark	as,are
R2346	T3590	T3561	advcl	are,known
R2347	T3591	T3590	nsubj	cells,are
R2348	T3592	T3591	prep	from,cells
R2349	T3593	T3594	det	a,model
R235	T332	T325	acl	affect,potential
R2350	T3594	T3592	pobj	model,from
R2351	T3595	T3594	amod	homozygous,model
R2352	T3596	T3594	amod	viable,model
R2353	T3597	T3598	nmod	XpdXPCS,XPCS
R2354	T3598	T3594	nmod	XPCS,model
R2355	T3599	T3598	punct	/,XPCS
R2356	T3600	T3601	punct	(,G602D
R2357	T3601	T3598	parataxis	G602D,XPCS
R2358	T3602	T3601	compound	XPDG602D,G602D
R2359	T3603	T3601	punct	/,G602D
R236	T333	T334	preconj	both,plasticity
R2360	T3604	T3601	punct	),G602D
R2361	T3605	T3594	compound	mouse,model
R2362	T3606	T3607	punct	(,4A
R2363	T3607	T3590	parataxis	4A,are
R2364	T3608	T3607	compound	Figure,4A
R2365	T3609	T3607	punct	", ",4A
R2366	T3610	T3611	amod	dotted,line
R2367	T3611	T3607	appos	line,4A
R2368	T3612	T3607	punct	),4A
R2369	T3613	T3614	punct	[,23
R237	T334	T332	dobj	plasticity,affect
R2370	T3614	T3561	parataxis	23,known
R2371	T3615	T3614	punct	],23
R2372	T3616	T3561	punct	.,known
R2373	T3618	T3619	advmod	Thus,represents
R2374	T3620	T3619	punct	", ",represents
R2375	T3621	T3622	det	the,survival
R2376	T3622	T3619	nsubj	survival,represents
R2377	T3623	T3622	prep	of,survival
R2378	T3624	T3625	nmod	XpdTTD,†XPCS
R2379	T3625	T3627	nmod	†XPCS,cells
R238	T335	T334	amod	normal,plasticity
R2380	T3626	T3625	punct	/,†XPCS
R2381	T3627	T3623	pobj	cells,of
R2382	T3628	T3625	punct	(,†XPCS
R2383	T3629	T3625	cc	and,†XPCS
R2384	T3630	T3631	compound	XpdTTD,†XP
R2385	T3631	T3625	conj	†XP,†XPCS
R2386	T3632	T3631	punct	/,†XP
R2387	T3633	T3627	punct	),cells
R2388	T3634	T3619	advmod	likely,represents
R2389	T3635	T3636	det	a,level
R239	T336	T335	cc	and,normal
R2390	T3636	T3619	dobj	level,represents
R2391	T3637	T3636	prep	of,level
R2392	T3638	T3639	compound	UV,resistance
R2393	T3639	T3637	pobj	resistance,of
R2394	T3640	T3641	dep	that,impart
R2395	T3641	T3636	relcl	impart,level
R2396	T3642	T3643	preconj	neither,allele
R2397	T3643	T3641	nsubj	allele,impart
R2398	T3644	T3643	amod	mutant,allele
R2399	T3645	T3641	aux	can,impart
R24	T110	T111	det	the,gene
R240	T337	T335	conj	pathological,normal
R2400	T3646	T3641	prep	on,impart
R2401	T3647	T3648	poss	its,own
R2402	T3648	T3646	pobj	own,on
R2403	T3649	T3650	punct	(,Table
R2404	T3650	T3619	parataxis	Table,represents
R2405	T3651	T3650	nummod	2,Table
R2406	T3652	T3650	punct	),Table
R2407	T3653	T3619	punct	.,represents
R2408	T3655	T3656	amod	Significant,effects
R2409	T3656	T3657	nsubjpass	effects,observed
R241	T338	T334	amod	phenotypic,plasticity
R2410	T3658	T3656	prep	of,effects
R2411	T3659	T3660	compound	compound,heterozygosity
R2412	T3660	T3658	pobj	heterozygosity,of
R2413	T3661	T3656	prep	on,effects
R2414	T3662	T3663	compound	NER,subpathways
R2415	T3663	T3661	pobj	subpathways,on
R2416	T3664	T3656	amod	relative,effects
R2417	T3665	T3664	prep	to,relative
R2418	T3666	T3667	compound	XpdTTD,KO
R2419	T3667	T3669	compound	KO,cells
R242	T339	T332	prep	in,affect
R2420	T3668	T3667	punct	/,KO
R2421	T3669	T3665	pobj	cells,to
R2422	T3670	T3657	auxpass	were,observed
R2423	T3671	T3657	prep	in,observed
R2424	T3672	T3673	compound	XpdTTD,†XP
R2425	T3673	T3675	compound	†XP,cells
R2426	T3674	T3673	punct	/,†XP
R2427	T3675	T3671	pobj	cells,in
R2428	T3676	T3671	cc	but,in
R2429	T3677	T3678	advmod	only,for
R243	T340	T339	pobj	mammals,in
R2430	T3678	T3671	conj	for,in
R2431	T3679	T3680	compound	UV,UDS
R2432	T3680	T3682	compound	UDS,activity
R2433	T3681	T3680	punct	-,UDS
R2434	T3682	T3678	pobj	activity,for
R2435	T3683	T3657	punct	.,observed
R2436	T3685	T3686	advmod	Finally,exhibited
R2437	T3687	T3686	punct	", ",exhibited
R2438	T3688	T3686	nsubj	none,exhibited
R2439	T3689	T3688	prep	of,none
R244	T341	T308	punct	.,suggest
R2440	T3690	T3691	det	the,combinations
R2441	T3691	T3689	pobj	combinations,of
R2442	T3692	T3691	amod	mutant,combinations
R2443	T3693	T3691	compound	TFIIH,combinations
R2444	T3694	T3691	punct	(,combinations
R2445	T3695	T3691	acl	carrying,combinations
R2446	T3696	T3695	dobj	alterations,carrying
R2447	T3697	T3696	acl	associated,alterations
R2448	T3698	T3697	prep	with,associated
R2449	T3699	T3698	pobj	TTD,with
R2450	T3700	T3701	punct	[,XPDR722W
R2451	T3701	T3699	parataxis	XPDR722W,TTD
R2452	T3702	T3701	punct	],XPDR722W
R2453	T3703	T3699	punct	", ",TTD
R2454	T3704	T3699	conj	XPCS,TTD
R2455	T3705	T3706	punct	[,XPDG602D
R2456	T3706	T3704	parataxis	XPDG602D,XPCS
R2457	T3707	T3706	punct	],XPDG602D
R2458	T3708	T3704	punct	", ",XPCS
R2459	T3709	T3704	cc	or,XPCS
R246	T565	T566	amod	Interallelic,complementation
R2460	T3710	T3704	conj	XP,XPCS
R2461	T3711	T3712	punct	[,XPDR683W
R2462	T3712	T3710	parataxis	XPDR683W,XP
R2463	T3713	T3712	punct	],XPDR683W
R2464	T3714	T3686	punct	),exhibited
R2465	T3715	T3686	dobj	synergism,exhibited
R2466	T3716	T3686	prep	in,exhibited
R2467	T3717	T3718	det	an,reaction
R2468	T3718	T3716	pobj	reaction,in
R2469	T3719	T3720	advmod	in,vitro
R247	T566	T567	nsubjpass	complementation,defined
R2470	T3720	T3718	amod	vitro,reaction
R2471	T3721	T3718	compound	NER,reaction
R2472	T3722	T3718	acl	reconstituted,reaction
R2473	T3723	T3722	prep	with,reconstituted
R2474	T3724	T3725	amod	different,complexes
R2475	T3725	T3723	pobj	complexes,with
R2476	T3726	T3725	amod	mutant,complexes
R2477	T3727	T3725	compound	TFIIH,complexes
R2478	T3728	T3729	punct	(,4D
R2479	T3729	T3686	parataxis	4D,exhibited
R248	T568	T567	auxpass	is,defined
R2480	T3730	T3729	compound	Figure,4D
R2481	T3731	T3729	punct	),4D
R2482	T3732	T3686	punct	.,exhibited
R2483	T3734	T3735	advcl	Taken,are
R2484	T3736	T3734	advmod	together,Taken
R2485	T3737	T3735	punct	", ",are
R2486	T3738	T3739	det	these,data
R2487	T3739	T3735	nsubj	data,are
R2488	T3740	T3735	acomp	consistent,are
R2489	T3741	T3740	prep	with,consistent
R249	T569	T567	prep	as,defined
R2490	T3742	T3743	amod	interallelic,complementation
R2491	T3743	T3741	pobj	complementation,with
R2492	T3744	T3743	prep	of,complementation
R2493	T3745	T3746	compound	UV,sensitivity
R2494	T3746	T3744	pobj	sensitivity,of
R2495	T3747	T3743	prep	in,complementation
R2496	T3748	T3747	pobj	cells,in
R2497	T3749	T3735	cc	but,are
R2498	T3750	T3735	conj	underscore,are
R2499	T3751	T3752	det	the,lack
R25	T111	T109	pobj	gene,of
R250	T570	T571	det	the,ability
R2500	T3752	T3750	dobj	lack,underscore
R2501	T3753	T3752	prep	of,lack
R2502	T3754	T3755	det	any,correlation
R2503	T3755	T3753	pobj	correlation,of
R2504	T3756	T3755	prep	between,correlation
R2505	T3757	T3758	npadvmod	UV,related
R2506	T3758	T3760	amod	related,characteristics
R2507	T3759	T3758	punct	-,related
R2508	T3760	T3756	pobj	characteristics,between
R2509	T3761	T3760	compound	repair,characteristics
R251	T571	T569	pobj	ability,as
R2510	T3762	T3760	cc	and,characteristics
R2511	T3763	T3764	compound	TTD,phenotypes
R2512	T3764	T3760	conj	phenotypes,characteristics
R2513	T3765	T3764	compound	progeroid,phenotypes
R2514	T3766	T3755	prep	in,correlation
R2515	T3767	T3768	compound	animal,models
R2516	T3768	T3766	pobj	models,in
R2517	T3769	T3735	punct	.,are
R2518	T3778	T3779	nsubj	sk,e
R2519	T3779	T3780	ccomp	e,t
R252	T572	T571	prep	of,ability
R2520	T3781	T3779	dobj	d,e
R2521	T3782	T3781	prep	wh,d
R2522	T3783	T3780	nsubj	e,t
R2523	T3789	T3790	det	h,e
R2524	T3798	T3797	cc	and,†XPCS
R2525	T3799	T3800	compound	Xpd,†XP
R2526	T3800	T3797	conj	†XP,†XPCS
R2527	T3801	T3802	amod	a,l
R2528	T3804	T3805	nsubj	l,e
R2529	T3806	T3805	dobj	les,e
R253	T573	T574	nummod	two,alleles
R2530	T3812	T3811	pobj	e,it
R2531	T3817	T3818	amod	re,a
R2532	T3821	T3820	cc	d,e
R2533	T3822	T3820	conj	m,e
R2534	T3826	T3825	compound	RNA,levels
R2535	T3827	T3824	punct	", ",ameliorated
R2536	T3828	T3829	compound	TTD,symptoms
R2537	T3829	T3824	dobj	symptoms,ameliorated
R2538	T3830	T3824	prep	by,ameliorated
R2539	T3831	T3832	amod	increasing,levels
R254	T574	T572	pobj	alleles,of
R2540	T3832	T3830	pobj	levels,by
R2541	T3833	T3832	amod	overall,levels
R2542	T3834	T3832	compound	TFIIH,levels
R2543	T3835	T3824	prep	in,ameliorated
R2544	T3836	T3837	nmod	compound,cells
R2545	T3837	T3835	pobj	cells,in
R2546	T3838	T3837	amod	heterozygous,cells
R2547	T3839	T3840	nmod	XpdTTD, †XPCS
R2548	T3840	T3837	nmod	†XPCS,cells
R2549	T3841	T3840	punct	/, †XPCS
R255	T575	T576	advmod	differentially,mutated
R2550	T3842	T3840	cc	and, †XPCS
R2551	T3843	T3844	compound	XpdTTD, †XP
R2552	T3844	T3840	conj	†XP, †XPCS
R2553	T3845	T3844	punct	/, †XP
R2554	T3848	T3849	advmod	Previously,shown
R2555	T3850	T3849	punct	", ",shown
R2556	T3851	T3849	advcl	using,shown
R2557	T3852	T3853	amod	comparative,immunohistochemistry
R2558	T3853	T3851	dobj	immunohistochemistry,using
R2559	T3854	T3849	punct	", ",shown
R256	T576	T574	amod	mutated,alleles
R2560	T3855	T3849	nsubj	we,shown
R2561	T3856	T3855	cc	and,we
R2562	T3857	T3855	conj	others,we
R2563	T3858	T3849	aux	have,shown
R2564	T3859	T3860	det	an,reduction
R2565	T3860	T3849	dobj	reduction,shown
R2566	T3861	T3862	quantmod	up,70
R2567	T3862	T3864	nummod	70,%
R2568	T3863	T3862	quantmod	to,70
R2569	T3864	T3860	compound	%,reduction
R257	T577	T578	aux	to,function
R2570	T3865	T3860	prep	of,reduction
R2571	T3866	T3867	compound	TFIIH,levels
R2572	T3867	T3865	pobj	levels,of
R2573	T3868	T3867	prep	in,levels
R2574	T3869	T3870	amod	primary,fibroblasts
R2575	T3870	T3868	pobj	fibroblasts,in
R2576	T3871	T3870	prep	from,fibroblasts
R2577	T3872	T3871	pobj	patients,from
R2578	T3873	T3872	prep	with,patients
R2579	T3874	T3873	pobj	TTD,with
R258	T578	T571	acl	function,ability
R2580	T3875	T3860	prep	compared,reduction
R2581	T3876	T3875	prep	with,compared
R2582	T3877	T3878	compound	wt,controls
R2583	T3878	T3876	pobj	controls,with
R2584	T3879	T3860	prep	due,reduction
R2585	T3880	T3879	pcomp	to,due
R2586	T3881	T3882	amod	reduced,stability
R2587	T3882	T3879	pobj	stability,due
R2588	T3883	T3884	punct	[,17
R2589	T3884	T3849	parataxis	17,shown
R259	T579	T578	advmod	better,function
R2590	T3885	T3884	nummod	16,17
R2591	T3886	T3884	punct	",",17
R2592	T3887	T3884	punct	],17
R2593	T3888	T3849	punct	.,shown
R2594	T3890	T3891	prep	Despite,reduced
R2595	T3892	T3890	pobj	overexpression,Despite
R2596	T3893	T3892	prep	of,overexpression
R2597	T3894	T3893	pobj	mRNA,of
R2598	T3895	T3894	prep	from,mRNA
R2599	T3896	T3897	det	the,allele
R26	T112	T111	amod	same,gene
R260	T580	T578	advmod	together,function
R2600	T3897	T3895	pobj	allele,from
R2601	T3898	T3897	compound	XpdTTD,allele
R2602	T3899	T3892	amod	relative,overexpression
R2603	T3900	T3899	prep	to,relative
R2604	T3901	T3902	det	the,allele
R2605	T3902	T3900	pobj	allele,to
R2606	T3903	T3902	compound	wt,allele
R2607	T3904	T3905	punct	(,1E
R2608	T3905	T3892	parataxis	1E,overexpression
R2609	T3906	T3905	compound	Figure,1E
R261	T581	T582	mark	than,can
R2610	T3907	T3905	punct	),1E
R2611	T3908	T3891	punct	", ",reduced
R2612	T3909	T3910	compound	TFIIH,levels
R2613	T3910	T3891	nsubjpass	levels,reduced
R2614	T3911	T3910	compound	protein,levels
R2615	T3912	T3891	auxpass	were,reduced
R2616	T3913	T3891	prep	by,reduced
R2617	T3914	T3915	nummod	50,%
R2618	T3915	T3913	pobj	%,by
R2619	T3916	T3891	prep	in,reduced
R262	T582	T578	advcl	can,function
R2620	T3917	T3918	amod	primary,fibroblasts
R2621	T3918	T3916	pobj	fibroblasts,in
R2622	T3919	T3918	compound	mouse,fibroblasts
R2623	T3920	T3921	compound	XpdTTD,TTD
R2624	T3921	T3918	compound	TTD,fibroblasts
R2625	T3922	T3921	punct	/,TTD
R2626	T3923	T3924	punct	(,4E
R2627	T3924	T3891	parataxis	4E,reduced
R2628	T3925	T3924	compound	Figure,4E
R2629	T3926	T3924	cc	and,4E
R263	T583	T582	nsubj	either,can
R2630	T3927	T3924	conj	4F,4E
R2631	T3928	T3924	punct	),4E
R2632	T3929	T3891	punct	", ",reduced
R2633	T3930	T3931	advmod	thereby,mimicking
R2634	T3931	T3891	advcl	mimicking,reduced
R2635	T3932	T3933	det	the,situation
R2636	T3933	T3931	dobj	situation,mimicking
R2637	T3934	T3931	prep	in,mimicking
R2638	T3935	T3936	amod	human,patients
R2639	T3936	T3934	pobj	patients,in
R264	T584	T582	prep	on,can
R2640	T3937	T3936	prep	with,patients
R2641	T3938	T3937	pobj	TTD,with
R2642	T3939	T3891	punct	.,reduced
R2643	T3941	T3942	prep	In,observed
R2644	T3943	T3941	pobj	accordance,In
R2645	T3944	T3943	prep	with,accordance
R2646	T3945	T3946	det	the,dosage
R2647	T3946	T3944	pobj	dosage,with
R2648	T3947	T3946	compound	gene,dosage
R2649	T3948	T3942	punct	", ",observed
R265	T585	T586	poss	its,own
R2650	T3949	T3950	det	a,reduction
R2651	T3950	T3942	nsubjpass	reduction,observed
R2652	T3951	T3950	amod	further,reduction
R2653	T3952	T3950	prep	of,reduction
R2654	T3953	T3954	quantmod	up,70
R2655	T3954	T3956	nummod	70,%
R2656	T3955	T3954	quantmod	to,70
R2657	T3956	T3952	pobj	%,of
R2658	T3957	T3956	prep	of,%
R2659	T3958	T3959	det	the,level
R266	T586	T584	pobj	own,on
R2660	T3959	T3957	pobj	level,of
R2661	T3960	T3959	compound	wt,level
R2662	T3961	T3942	auxpass	was,observed
R2663	T3962	T3942	prep	in,observed
R2664	T3963	T3964	amod	hemizygous,cells
R2665	T3964	T3962	pobj	cells,in
R2666	T3965	T3966	compound	XpdTTD,KO
R2667	T3966	T3964	compound	KO,cells
R2668	T3967	T3966	punct	/,KO
R2669	T3968	T3942	punct	.,observed
R267	T587	T567	punct	.,defined
R2670	T3970	T3971	advcl	Consistent,was
R2671	T3972	T3970	prep	with,Consistent
R2672	T3973	T3974	amod	low,levels
R2673	T3974	T3972	pobj	levels,with
R2674	T3975	T3976	compound	mRNA,expression
R2675	T3976	T3974	compound	expression,levels
R2676	T3977	T3971	punct	", ",was
R2677	T3978	T3979	preconj	neither,allele
R2678	T3979	T3971	nsubj	allele,was
R2679	T3980	T3981	det	the,Xpd†XPCS
R268	T589	T590	prep	Despite,considered
R2680	T3981	T3979	nmod	Xpd†XPCS,allele
R2681	T3982	T3981	cc	nor,Xpd†XPCS
R2682	T3983	T3984	det	the,Xpd†XP
R2683	T3984	T3981	conj	Xpd†XP,Xpd†XPCS
R2684	T3985	T3971	acomp	able,was
R2685	T3986	T3987	aux	to,restore
R2686	T3987	T3985	xcomp	restore,able
R2687	T3988	T3989	compound	TFIIH,abundance
R2688	T3989	T3987	dobj	abundance,restore
R2689	T3990	T3987	prep	to,restore
R269	T591	T592	poss	its,universality
R2690	T3991	T3992	compound	wt,levels
R2691	T3992	T3990	pobj	levels,to
R2692	T3993	T3987	prep	in,restore
R2693	T3994	T3995	compound	XpdTTD,cells
R2694	T3995	T3993	pobj	cells,in
R2695	T3996	T3995	compound	compound,cells
R2696	T3997	T3995	compound	heterozygote,cells
R2697	T3998	T3999	punct	(,4E
R2698	T3999	T3971	parataxis	4E,was
R2699	T4000	T3999	compound	Figure,4E
R27	T113	T97	punct	", ",is
R270	T592	T589	pobj	universality,Despite
R2700	T4001	T3999	cc	and,4E
R2701	T4002	T3999	conj	4F,4E
R2702	T4003	T3999	punct	),4E
R2703	T4004	T3971	punct	.,was
R2704	T4006	T4007	advmod	Thus,were
R2705	T4008	T4007	punct	", ",were
R2706	T4009	T4010	det	the,survival
R2707	T4010	T4007	nsubj	survival,were
R2708	T4011	T4010	amod	improved,survival
R2709	T4012	T4010	compound	UV,survival
R271	T593	T592	amod	near,universality
R2710	T4013	T4010	acl	observed,survival
R2711	T4014	T4013	prep	in,observed
R2712	T4015	T4016	compound	compound,cells
R2713	T4016	T4014	pobj	cells,in
R2714	T4017	T4016	compound	heterozygote,cells
R2715	T4018	T4019	punct	(,4A
R2716	T4019	T4013	parataxis	4A,observed
R2717	T4020	T4019	compound	Figure,4A
R2718	T4021	T4019	punct	),4A
R2719	T4022	T4013	cc	and,observed
R272	T594	T592	prep	in,universality
R2720	T4023	T4024	advmod	likely,rescue
R2721	T4024	T4013	conj	rescue,observed
R2722	T4025	T4024	det	the,rescue
R2723	T4026	T4024	prep	of,rescue
R2724	T4027	T4028	compound	TTD,symptoms
R2725	T4028	T4026	pobj	symptoms,of
R2726	T4029	T4028	compound	progeroid,symptoms
R2727	T4030	T4031	punct	(,Figure
R2728	T4031	T4024	parataxis	Figure,rescue
R2729	T4032	T4031	nummod	3,Figure
R273	T595	T596	amod	lower,organisms
R2730	T4033	T4031	punct	),Figure
R2731	T4034	T4007	neg	not,were
R2732	T4035	T4007	prep	due,were
R2733	T4036	T4035	pcomp	to,due
R2734	T4037	T4035	pobj	normalisation,due
R2735	T4038	T4037	prep	of,normalisation
R2736	T4039	T4040	compound	TFIIH,levels
R2737	T4040	T4038	pobj	levels,of
R2738	T4041	T4007	punct	", ",were
R2739	T4042	T4007	advcl	suggesting,were
R274	T596	T594	pobj	organisms,in
R2740	T4043	T4044	advmod	a,qualitative
R2741	T4044	T4045	amod	qualitative,effect
R2742	T4045	T4042	dobj	effect,suggesting
R2743	T4046	T4047	advmod	rather,than
R2744	T4047	T4044	cc	than,qualitative
R2745	T4048	T4049	advmod	a,quantitative
R2746	T4049	T4044	conj	quantitative,qualitative
R2747	T4050	T4045	prep	on,effect
R2748	T4051	T4052	det	these,phenotypes
R2749	T4052	T4050	pobj	phenotypes,on
R275	T597	T598	punct	[,1
R2750	T4053	T4054	advmod	in,vivo
R2751	T4054	T4045	advmod	vivo,effect
R2752	T4055	T4007	punct	.,were
R2753	T4057	T4058	prep	In,affect
R2754	T4059	T4057	pobj	contrast,In
R2755	T4060	T4058	punct	", ",affect
R2756	T4061	T4062	det	the,level
R2757	T4062	T4058	nsubj	level,affect
R2758	T4063	T4062	prep	of,level
R2759	T4064	T4065	compound	XPCS,expression
R276	T598	T596	parataxis	1,organisms
R2760	T4065	T4063	pobj	expression,of
R2761	T4066	T4065	compound	mRNA,expression
R2762	T4067	T4058	aux	did,affect
R2763	T4068	T4069	det	the,ability
R2764	T4069	T4058	dobj	ability,affect
R2765	T4070	T4069	prep	of,ability
R2766	T4071	T4072	det	the,protein
R2767	T4072	T4070	pobj	protein,of
R2768	T4073	T4072	amod	encoded,protein
R2769	T4074	T4072	punct	(,protein
R277	T599	T598	punct	],1
R2770	T4075	T4072	appos	XPDG602D,protein
R2771	T4076	T4069	punct	),ability
R2772	T4077	T4078	aux	to,restore
R2773	T4078	T4069	acl	restore,ability
R2774	T4079	T4080	det	the,phenotype
R2775	T4080	T4078	dobj	phenotype,restore
R2776	T4081	T4080	compound	TTD,phenotype
R2777	T4082	T4080	compound	hair,phenotype
R2778	T4083	T4078	prep	to,restore
R2779	T4084	T4083	amod	normal,to
R278	T600	T590	punct	", ",considered
R2780	T4085	T4058	punct	.,affect
R2781	T4087	T4088	advmod	Notably,had
R2782	T4089	T4088	punct	", ",had
R2783	T4090	T4091	compound	XpdTTD, †XPCS
R2784	T4091	T4093	compound	†XPCS,animals
R2785	T4092	T4091	punct	/, †XPCS
R2786	T4093	T4088	nsubj	animals,had
R2787	T4094	T4095	det	a,phenotype
R2788	T4095	T4088	dobj	phenotype,had
R2789	T4096	T4095	amod	partial,phenotype
R279	T601	T602	poss	its,potential
R2790	T4097	T4095	compound	TTD,phenotype
R2791	T4098	T4095	compound	hair,phenotype
R2792	T4099	T4095	punct	", ",phenotype
R2793	T4100	T4095	acl	correlating,phenotype
R2794	T4101	T4100	prep	with,correlating
R2795	T4102	T4103	amod	low,levels
R2796	T4103	T4101	pobj	levels,with
R2797	T4104	T4103	prep	of,levels
R2798	T4105	T4106	compound	Xpd†XPCS,expression
R2799	T4106	T4104	pobj	expression,of
R28	T115	T97	acomp	common,is
R280	T602	T590	nsubjpass	potential,considered
R2800	T4107	T4088	punct	", ",had
R2801	T4108	T4109	mark	whereas,had
R2802	T4109	T4088	advcl	had,had
R2803	T4110	T4111	compound	XpdTTD,XPCS
R2804	T4111	T4113	compound	XPCS,animals
R2805	T4112	T4111	punct	/,XPCS
R2806	T4113	T4109	nsubj	animals,had
R2807	T4114	T4115	compound	wt,hair
R2808	T4115	T4109	dobj	hair,had
R2809	T4116	T4115	punct	", ",hair
R281	T603	T604	aux	to,contribute
R2810	T4117	T4115	acl	correlating,hair
R2811	T4118	T4117	prep	with,correlating
R2812	T4119	T4120	amod	normal,levels
R2813	T4120	T4118	pobj	levels,with
R2814	T4121	T4120	compound	expression,levels
R2815	T4122	T4120	prep	from,levels
R2816	T4123	T4124	det	the,allele
R2817	T4124	T4122	pobj	allele,from
R2818	T4125	T4124	amod	viable,allele
R2819	T4126	T4124	compound	XpdXPCS,allele
R282	T604	T602	acl	contribute,potential
R2820	T4127	T4128	punct	(,Table
R2821	T4128	T4088	parataxis	Table,had
R2822	T4129	T4128	nummod	2,Table
R2823	T4130	T4128	cc	and,Table
R2824	T4131	T4132	amod	unpublished,data
R2825	T4132	T4128	conj	data,Table
R2826	T4133	T4128	punct	),Table
R2827	T4134	T4088	punct	.,had
R2828	T4136	T4137	advmod	Thus,affected
R2829	T4138	T4137	punct	", ",affected
R283	T605	T604	prep	to,contribute
R2830	T4139	T4140	det	the,range
R2831	T4140	T4137	nsubj	range,affected
R2832	T4141	T4140	prep	of,range
R2833	T4142	T4143	compound	expression,levels
R2834	T4143	T4141	pobj	levels,of
R2835	T4144	T4140	prep	from,range
R2836	T4145	T4146	det	these,alleles
R2837	T4146	T4144	pobj	alleles,from
R2838	T4147	T4146	nummod	two,alleles
R2839	T4148	T4146	amod	mutant,alleles
R284	T606	T607	amod	clinical,heterogeneity
R2840	T4149	T4150	poss	their,ability
R2841	T4150	T4137	dobj	ability,affected
R2842	T4151	T4152	aux	to,complement
R2843	T4152	T4150	acl	complement,ability
R2844	T4153	T4154	det	some,phenotypes
R2845	T4154	T4152	dobj	phenotypes,complement
R2846	T4155	T4156	punct	(,hair
R2847	T4156	T4154	parataxis	hair,phenotypes
R2848	T4157	T4156	punct	),hair
R2849	T4158	T4137	punct	.,affected
R285	T607	T605	pobj	heterogeneity,to
R2850	T4160	T4161	det	An,overview
R2851	T4161	T4162	nsubjpass	overview,presented
R2852	T4163	T4161	prep	of,overview
R2853	T4164	T4165	det	the,relationships
R2854	T4165	T4163	pobj	relationships,of
R2855	T4166	T4165	amod	functional,relationships
R2856	T4167	T4165	prep	between,relationships
R2857	T4168	T4169	compound	Xpd,alleles
R2858	T4169	T4167	pobj	alleles,between
R2859	T4170	T4169	punct	", ",alleles
R286	T608	T607	prep	in,heterogeneity
R2860	T4171	T4169	conj	phenotypes,alleles
R2861	T4172	T4171	punct	", ",phenotypes
R2862	T4173	T4171	cc	and,phenotypes
R2863	T4174	T4175	det	the,function
R2864	T4175	T4171	conj	function,phenotypes
R2865	T4176	T4175	amod	presumed,function
R2866	T4177	T4175	amod	underlying,function
R2867	T4178	T4175	compound	TFIIH,function
R2868	T4179	T4165	prep	in,relationships
R2869	T4180	T4179	pobj	mice,in
R287	T609	T610	amod	human,disease
R2870	T4181	T4180	cc	and,mice
R2871	T4182	T4180	conj	cells,mice
R2872	T4183	T4162	auxpass	is,presented
R2873	T4184	T4162	prep	in,presented
R2874	T4185	T4184	pobj	Table,in
R2875	T4186	T4185	nummod	2,Table
R2876	T4187	T4162	punct	.,presented
R2877	T4260	T4259	prep	of,Dissection
R2878	T4261	T4262	amod	Biallelic,Effects
R2879	T4262	T4260	pobj	Effects,of
R288	T610	T608	pobj	disease,in
R2880	T4263	T4259	prep	from,Dissection
R2881	T4264	T4265	amod	other,Determinants
R2882	T4265	T4263	pobj	Determinants,from
R2883	T4266	T4265	prep	of,Determinants
R2884	T4267	T4266	pobj	Phenotype,of
R2885	T4269	T4270	mark	Although,postulated
R2886	T4270	T4293	advcl	postulated,been
R2887	T4271	T4272	amod	phenotypic,consequences
R2888	T4272	T4270	nsubjpass	consequences,postulated
R2889	T4273	T4272	punct	", ",consequences
R289	T611	T590	auxpass	is,considered
R2890	T4274	T4272	acl	referred,consequences
R2891	T4275	T4274	prep	to,referred
R2892	T4276	T4274	advmod	here,referred
R2893	T4277	T4274	prep	as,referred
R2894	T4278	T4279	amod	biallelic,effects
R2895	T4279	T4277	pobj	effects,as
R2896	T4280	T4272	punct	", ",consequences
R2897	T4281	T4272	acl	resulting,consequences
R2898	T4282	T4281	prep	from,resulting
R2899	T4283	T4284	nummod	two,alleles
R29	T116	T97	prep	in,is
R290	T612	T590	advmod	seldom,considered
R2900	T4284	T4282	pobj	alleles,from
R2901	T4285	T4284	amod	different,alleles
R2902	T4286	T4284	amod	mutant,alleles
R2903	T4287	T4284	prep	in,alleles
R2904	T4288	T4289	compound	compound,patients
R2905	T4289	T4287	pobj	patients,in
R2906	T4290	T4289	compound	heterozygote,patients
R2907	T4291	T4270	aux	have,postulated
R2908	T4292	T4270	auxpass	been,postulated
R2909	T4294	T4293	punct	", ",been
R291	T613	T590	punct	.,considered
R2910	T4295	T4296	amod	such,effects
R2911	T4296	T4293	nsubj	effects,been
R2912	T4297	T4293	aux	have,been
R2913	T4298	T4293	advmod	historically,been
R2914	T4299	T4293	acomp	difficult,been
R2915	T4300	T4301	aux	to,distinguish
R2916	T4301	T4299	xcomp	distinguish,difficult
R2917	T4302	T4301	prep	from,distinguish
R2918	T4303	T4304	det	the,influence
R2919	T4304	T4302	pobj	influence,from
R292	T615	T616	nsubjpass	Evidence,limited
R2920	T4305	T4304	prep	of,influence
R2921	T4306	T4305	pobj	environment,of
R2922	T4307	T4306	cc	and,environment
R2923	T4308	T4309	amod	genetic,background
R2924	T4309	T4306	conj	background,environment
R2925	T4310	T4293	punct	.,been
R2926	T4312	T4313	nsubj	We,used
R2927	T4314	T4315	det	a,system
R2928	T4315	T4313	dobj	system,used
R2929	T4316	T4317	advmod	genetically,defined
R293	T617	T615	prep	of,Evidence
R2930	T4317	T4315	amod	defined,system
R2931	T4318	T4315	amod	mammalian,system
R2932	T4319	T4315	compound	model,system
R2933	T4320	T4313	prep	under,used
R2934	T4321	T4322	amod	controlled,conditions
R2935	T4322	T4320	pobj	conditions,under
R2936	T4323	T4322	amod	environmental,conditions
R2937	T4324	T4325	aux	to,reveal
R2938	T4325	T4313	advcl	reveal,used
R2939	T4326	T4327	amod	phenotypic,effects
R294	T618	T619	amod	interallelic,complementation
R2940	T4327	T4325	dobj	effects,reveal
R2941	T4328	T4327	amod	attributable,effects
R2942	T4329	T4330	advmod	specifically,to
R2943	T4330	T4328	prep	to,attributable
R2944	T4331	T4330	pobj	combinations,to
R2945	T4332	T4331	prep	of,combinations
R2946	T4333	T4334	advmod	differentially,mutated
R2947	T4334	T4335	amod	mutated,alleles
R2948	T4335	T4332	pobj	alleles,of
R2949	T4336	T4335	compound	Xpd,alleles
R295	T619	T617	pobj	complementation,of
R2950	T4337	T4313	punct	.,used
R2951	T4339	T4340	det	The,effects
R2952	T4340	T4343	nsubj	effects,were
R2953	T4341	T4340	amod	observed,effects
R2954	T4342	T4340	amod	biallelic,effects
R2955	T4344	T4343	prep	of,were
R2956	T4345	T4346	nummod	three,types
R2957	T4346	T4344	pobj	types,of
R2958	T4347	T4346	amod	general,types
R2959	T4348	T4343	punct	.,were
R296	T620	T619	prep	at,complementation
R2960	T4350	T4351	prep	In,determined
R2961	T4352	T4353	det	the,first
R2962	T4353	T4350	pobj	first,In
R2963	T4354	T4351	punct	", ",determined
R2964	T4355	T4356	det	the,allele
R2965	T4356	T4351	nsubj	allele,determined
R2966	T4357	T4356	acl	associated,allele
R2967	T4358	T4357	prep	in,associated
R2968	T4359	T4360	det	a,state
R2969	T4360	T4358	pobj	state,in
R297	T621	T622	advmod	clinically,relevant
R2970	T4361	T4360	amod	homozygous,state
R2971	T4362	T4357	prep	with,associated
R2972	T4363	T4364	det	a,phenotype
R2973	T4364	T4362	pobj	phenotype,with
R2974	T4365	T4366	advmod	closer,to
R2975	T4366	T4364	amod	to,phenotype
R2976	T4367	T4366	pobj	wt,to
R2977	T4368	T4351	advmod	singularly,determined
R2978	T4369	T4370	det	the,outcome
R2979	T4370	T4351	dobj	outcome,determined
R298	T622	T623	amod	relevant,loci
R2980	T4371	T4370	amod	phenotypic,outcome
R2981	T4372	T4351	punct	", ",determined
R2982	T4373	T4374	det	a,phenomenon
R2983	T4374	T4351	npadvmod	phenomenon,determined
R2984	T4375	T4376	advmod	widely,known
R2985	T4376	T4374	acl	known,phenomenon
R2986	T4377	T4376	prep	in,known
R2987	T4378	T4379	amod	human,disease
R2988	T4379	T4377	pobj	disease,in
R2989	T4380	T4379	amod	recessive,disease
R299	T623	T620	pobj	loci,at
R2990	T4381	T4351	punct	.,determined
R2991	T4383	T4384	mark	Because,functioned
R2992	T4384	T4388	advcl	functioned,call
R2993	T4385	T4386	det	these,alleles
R2994	T4386	T4384	nsubj	alleles,functioned
R2995	T4387	T4386	compound	Xpd,alleles
R2996	T4389	T4384	prep	at,functioned
R2997	T4390	T4389	cc	or,at
R2998	T4391	T4389	conj	near,at
R2999	T4392	T4393	compound	wt,levels
R3	T88	T84	prep	in,Rescue
R30	T117	T118	amod	human,disease
R300	T624	T616	auxpass	is,limited
R3000	T4393	T4391	pobj	levels,near
R3001	T4394	T4384	prep	with,functioned
R3002	T4395	T4394	pobj	respect,with
R3003	T4396	T4395	prep	to,respect
R3004	T4397	T4398	det	a,function
R3005	T4398	T4396	pobj	function,to
R3006	T4399	T4398	amod	particular,function
R3007	T4400	T4388	punct	", ",call
R3008	T4401	T4388	nsubj	we,call
R3009	T4402	T4403	det	these,effects
R301	T625	T616	prep	to,limited
R3010	T4403	T4388	dobj	effects,call
R3011	T4404	T4388	punct	“,call
R3012	T4405	T4388	oprd	dominant,call
R3013	T4406	T4388	punct	”,call
R3014	T4407	T4388	punct	.,call
R3015	T4409	T4410	amod	Such,alleles
R3016	T4410	T4411	nsubjpass	alleles,referred
R3017	T4412	T4411	aux	can,referred
R3018	T4413	T4411	advmod	also,referred
R3019	T4414	T4411	auxpass	be,referred
R302	T626	T627	amod	biochemical,studies
R3020	T4415	T4411	prep	to,referred
R3021	T4416	T4411	prep	as,referred
R3022	T4417	T4418	punct	“,alleles
R3023	T4418	T4416	pobj	alleles,as
R3024	T4419	T4418	nmod	separation,alleles
R3025	T4420	T4419	prep	of,separation
R3026	T4421	T4420	pobj	function,of
R3027	T4422	T4418	punct	”,alleles
R3028	T4423	T4411	punct	", ",referred
R3029	T4424	T4425	mark	because,allow
R303	T627	T625	pobj	studies,to
R3030	T4425	T4411	advcl	allow,referred
R3031	T4426	T4425	nsubj	they,allow
R3032	T4427	T4425	dobj	dissection,allow
R3033	T4428	T4427	prep	of,dissection
R3034	T4429	T4430	det	the,roles
R3035	T4430	T4428	pobj	roles,of
R3036	T4431	T4430	prep	of,roles
R3037	T4432	T4433	amod	multifunctional,proteins
R3038	T4433	T4431	pobj	proteins,of
R3039	T4434	T4425	prep	in,allow
R304	T628	T626	cc	and,biochemical
R3040	T4435	T4436	amod	specific,phenotypes
R3041	T4436	T4434	pobj	phenotypes,in
R3042	T4437	T4411	punct	.,referred
R3043	T4439	T4440	advmod	Secondly,was
R3044	T4441	T4440	punct	", ",was
R3045	T4442	T4440	dep	highlighting,was
R3046	T4443	T4444	det	the,relevance
R3047	T4444	T4442	dobj	relevance,highlighting
R3048	T4445	T4444	amod	potential,relevance
R3049	T4446	T4444	prep	of,relevance
R305	T629	T630	npadvmod	cell,based
R3050	T4447	T4448	amod	current,findings
R3051	T4448	T4446	pobj	findings,of
R3052	T4449	T4444	prep	to,relevance
R3053	T4450	T4451	det	all,organisms
R3054	T4451	T4449	pobj	organisms,to
R3055	T4452	T4451	amod	diploid,organisms
R3056	T4453	T4451	prep	including,organisms
R3057	T4454	T4453	pobj	humans,including
R3058	T4455	T4456	det	the,observation
R3059	T4456	T4440	nsubj	observation,was
R306	T630	T626	conj	based,biochemical
R3060	T4457	T4458	mark	that,shift
R3061	T4458	T4456	acl	shift,observation
R3062	T4459	T4458	prep	in,shift
R3063	T4460	T4461	nummod	one,animal
R3064	T4461	T4459	pobj	animal,in
R3065	T4462	T4461	nmod	compound,animal
R3066	T4463	T4461	amod	heterozygous,animal
R3067	T4464	T4458	punct	", ",shift
R3068	T4465	T4466	det	the,relationship
R3069	T4466	T4458	nsubj	relationship,shift
R307	T631	T630	punct	-,based
R3070	T4467	T4466	nmod	Xpd,relationship
R3071	T4468	T4466	amod	allelic,relationship
R3072	T4469	T4458	aux	could,shift
R3073	T4470	T4458	prep	from,shift
R3074	T4471	T4472	amod	A dominant,a recessive
R3075	T4472	T4470	pobj	a recessive,from
R3076	T4473	T4472	punct	\|,a recessive
R3077	T4474	T4470	prep	to,from
R3078	T4475	T4476	amod	A recessive,a dominant
R3079	T4476	T4474	pobj	a dominant,to
R308	T632	T627	prep	of,studies
R3080	T4477	T4476	punct	\|,a dominant
R3081	T4478	T4458	prep	with,shift
R3082	T4479	T4478	pobj	respect,with
R3083	T4480	T4479	prep	to,respect
R3084	T4481	T4482	amod	different,phenotypes
R3085	T4482	T4480	pobj	phenotypes,to
R3086	T4483	T4458	prep	in,shift
R3087	T4484	T4485	det	a,manner
R3088	T4485	T4483	pobj	manner,in
R3089	T4486	T4487	npadvmod	time,dependent
R309	T633	T634	det	a,handful
R3090	T4487	T4485	amod	dependent,manner
R3091	T4488	T4487	punct	-,dependent
R3092	T4489	T4487	cc	and,dependent
R3093	T4490	T4491	npadvmod	tissue,specific
R3094	T4491	T4487	conj	specific,dependent
R3095	T4492	T4491	punct	-,specific
R3096	T4493	T4494	punct	(,see
R3097	T4494	T4458	parataxis	see,shift
R3098	T4495	T4496	advmod	below,Table
R3099	T4496	T4494	dobj	Table,see
R31	T118	T116	pobj	disease,in
R310	T634	T632	pobj	handful,of
R3100	T4497	T4496	cc	and,Table
R3101	T4498	T4496	nummod	2,Table
R3102	T4499	T4494	punct	),see
R3103	T4500	T4440	punct	.,was
R3104	T4502	T4503	prep	In,produced
R3105	T4504	T4505	det	the,type
R3106	T4505	T4502	pobj	type,In
R3107	T4506	T4505	amod	third,type
R3108	T4507	T4505	prep	of,type
R3109	T4508	T4509	amod	biallelic,effect
R311	T635	T634	prep	of,handful
R3110	T4509	T4507	pobj	effect,of
R3111	T4510	T4505	punct	", ",type
R3112	T4511	T4505	acl	known,type
R3113	T4512	T4511	prep	as,known
R3114	T4513	T4514	amod	interallelic,complementation
R3115	T4514	T4512	pobj	complementation,as
R3116	T4515	T4503	punct	", ",produced
R3117	T4516	T4517	nummod	two,alleles
R3118	T4517	T4503	nsubj	alleles,produced
R3119	T4518	T4517	amod	mutant,alleles
R312	T636	T637	amod	metabolic,disorders
R3120	T4519	T4520	det	a,phenotype
R3121	T4520	T4503	dobj	phenotype,produced
R3122	T4521	T4522	advmod	closer,to
R3123	T4522	T4520	amod	to,phenotype
R3124	T4523	T4522	pobj	wt,to
R3125	T4524	T4525	mark	than,alone
R3126	T4525	T4522	advcl	alone,to
R3127	T4526	T4525	nsubj	either,alone
R3128	T4527	T4525	aux	could,alone
R3129	T4528	T4525	prep	in,alone
R313	T637	T635	pobj	disorders,of
R3130	T4529	T4530	det	a,state
R3131	T4530	T4528	pobj	state,in
R3132	T4531	T4532	advmod	homo,hemizygous
R3133	T4532	T4530	amod	hemizygous,state
R3134	T4533	T4532	punct	-,hemizygous
R3135	T4534	T4532	cc	or,hemizygous
R3136	T4535	T4503	punct	.,produced
R3137	T4537	T4538	mark	As,summarised
R3138	T4538	T4539	advcl	summarised,observed
R3139	T4540	T4538	prep	in,summarised
R314	T638	T637	prep	with,disorders
R3140	T4541	T4540	pobj	Table,in
R3141	T4542	T4541	nummod	2,Table
R3142	T4543	T4539	punct	", ",observed
R3143	T4544	T4539	nsubjpass	examples,observed
R3144	T4545	T4544	prep	of,examples
R3145	T4546	T4547	det	all,types
R3146	T4547	T4545	pobj	types,of
R3147	T4548	T4547	prep	of,types
R3148	T4549	T4550	amod	biallelic,effects
R3149	T4550	T4548	pobj	effects,of
R315	T639	T638	pobj	defects,with
R3150	T4551	T4539	auxpass	were,observed
R3151	T4552	T4539	prep	in,observed
R3152	T4553	T4554	det	a,variety
R3153	T4554	T4552	pobj	variety,in
R3154	T4555	T4554	prep	of,variety
R3155	T4556	T4557	npadvmod	Xpd,associated
R3156	T4557	T4559	amod	associated,phenotypes
R3157	T4558	T4557	punct	-,associated
R3158	T4559	T4555	pobj	phenotypes,of
R3159	T4560	T4554	punct	", ",variety
R316	T640	T639	prep	in,defects
R3160	T4561	T4554	acl	ranging,variety
R3161	T4562	T4561	prep	from,ranging
R3162	T4563	T4564	amod	brittle,hair
R3163	T4564	T4562	pobj	hair,from
R3164	T4565	T4562	prep	to,from
R3165	T4566	T4567	amod	segmental,progeria
R3166	T4567	T4565	pobj	progeria,to
R3167	T4568	T4539	punct	.,observed
R317	T641	T640	pobj	enzymes,in
R318	T642	T641	prep	including,enzymes
R3180	T4806	T4805	prep	in,TFIIH
R3181	T4807	T4806	pobj	Transcription,in
R3182	T4808	T4807	cc	and,Transcription
R3183	T4809	T4807	conj	Repair,Transcription
R3184	T4810	T4805	punct	: ,TFIIH
R3185	T4811	T4805	appos	Mechanisms,TFIIH
R3186	T4812	T4811	prep	of,Mechanisms
R3187	T4813	T4814	compound	XPD,Pleiotropy
R3188	T4814	T4812	pobj	Pleiotropy,of
R3189	T4815	T4814	compound	Disease,Pleiotropy
R319	T643	T644	compound	propinyl,CoA
R3190	T4817	T4818	nsubj	We,observed
R3191	T4819	T4818	dobj	differences,observed
R3192	T4820	T4819	prep	in,differences
R3193	T4821	T4822	det	the,ability
R3194	T4822	T4820	pobj	ability,in
R3195	T4823	T4822	prep	of,ability
R3196	T4824	T4823	pobj	XpdTTD,of
R3197	T4825	T4824	cc	versus,XpdTTD
R3198	T4826	T4827	amod	homozygous,alleles
R3199	T4827	T4824	conj	alleles,XpdTTD
R32	T119	T118	amod	recessive,disease
R320	T644	T646	compound	CoA,carboxylase
R3200	T4828	T4827	amod	lethal,alleles
R3201	T4829	T4827	nmod	Xpd†XPCS,alleles
R3202	T4830	T4829	cc	and,Xpd†XPCS
R3203	T4831	T4829	conj	Xpd†XP,Xpd†XPCS
R3204	T4832	T4833	aux	to,function
R3205	T4833	T4822	acl	function,ability
R3206	T4834	T4833	prep	in,function
R3207	T4835	T4836	nummod	two,phenotypes
R3208	T4836	T4834	pobj	phenotypes,in
R3209	T4837	T4838	npadvmod	transcription,related
R321	T645	T644	punct	-,CoA
R3210	T4838	T4836	amod	related,phenotypes
R3211	T4839	T4838	punct	-,related
R3212	T4840	T4836	acl	separated,phenotypes
R3213	T4841	T4840	prep	in,separated
R3214	T4842	T4843	det	the,organism
R3215	T4843	T4841	pobj	organism,in
R3216	T4844	T4840	prep	by,separated
R3217	T4845	T4846	preconj	both,time
R3218	T4846	T4844	pobj	time,by
R3219	T4847	T4846	cc	and,time
R322	T646	T642	pobj	carboxylase,including
R3220	T4848	T4846	conj	space,time
R3221	T4849	T4819	punct	: ,differences
R3222	T4850	T4851	amod	embryonic,lethality
R3223	T4851	T4819	appos	lethality,differences
R3224	T4852	T4851	cc	and,lethality
R3225	T4853	T4854	amod	terminal,differentiation
R3226	T4854	T4851	conj	differentiation,lethality
R3227	T4855	T4854	prep	of,differentiation
R3228	T4856	T4857	amod	enucleating,skin
R3229	T4857	T4855	pobj	skin,of
R323	T647	T648	punct	[,2
R3230	T4858	T4857	cc	and,skin
R3231	T4859	T4860	compound	blood,cells
R3232	T4860	T4857	conj	cells,skin
R3233	T4861	T4818	punct	.,observed
R3234	T4863	T4864	det	The,lethality
R3235	T4864	T4869	nsubj	lethality,reflects
R3236	T4865	T4866	nmod	preblastocyst,stage
R3237	T4866	T4864	nmod	stage,lethality
R3238	T4867	T4866	punct	-,stage
R3239	T4868	T4864	amod	homozygous,lethality
R324	T648	T646	parataxis	2,carboxylase
R3240	T4870	T4864	acl	shared,lethality
R3241	T4871	T4870	agent	by,shared
R3242	T4872	T4873	det	the,alleles
R3243	T4873	T4871	pobj	alleles,by
R3244	T4874	T4873	nmod	XpdKO,alleles
R3245	T4875	T4874	punct	", ",XpdKO
R3246	T4876	T4874	conj	Xpd†XPCS,XpdKO
R3247	T4877	T4876	punct	", ",Xpd†XPCS
R3248	T4878	T4876	cc	and,Xpd†XPCS
R3249	T4879	T4876	conj	Xpd†XP,Xpd†XPCS
R325	T649	T648	punct	],2
R3250	T4880	T4881	advmod	most,likely
R3251	T4881	T4869	advmod	likely,reflects
R3252	T4882	T4883	det	a,defect
R3253	T4883	T4869	dobj	defect,reflects
R3254	T4884	T4883	prep	in,defect
R3255	T4885	T4886	amod	basal,transcription
R3256	T4886	T4884	pobj	transcription,in
R3257	T4887	T4888	dep	that,is
R3258	T4888	T4883	relcl	is,defect
R3259	T4889	T4888	acomp	incompatible,is
R326	T650	T646	punct	", ",carboxylase
R3260	T4890	T4889	prep	with,incompatible
R3261	T4891	T4890	pobj	life,with
R3262	T4892	T4869	punct	.,reflects
R3263	T4894	T4895	prep	In,rescued
R3264	T4896	T4897	nmod	XpdTTD, †XPCS
R3265	T4897	T4899	nmod	†XPCS,mice
R3266	T4898	T4897	punct	/, †XPCS
R3267	T4899	T4894	pobj	mice,In
R3268	T4900	T4897	cc	and, †XPCS
R3269	T4901	T4902	compound	XpdTTD, †XP
R327	T651	T652	compound	argininosuccinate,lyase
R3270	T4902	T4897	conj	†XP, †XPCS
R3271	T4903	T4902	punct	/, †XP
R3272	T4904	T4899	nmod	compound,mice
R3273	T4905	T4899	amod	heterozygous,mice
R3274	T4906	T4895	punct	", ",rescued
R3275	T4907	T4908	amod	embryonic,lethality
R3276	T4908	T4895	nsubjpass	lethality,rescued
R3277	T4909	T4895	auxpass	was,rescued
R3278	T4910	T4895	advmod	fully,rescued
R3279	T4911	T4895	agent	by,rescued
R328	T652	T646	conj	lyase,carboxylase
R3280	T4912	T4913	det	the,allele
R3281	T4913	T4911	pobj	allele,by
R3282	T4914	T4913	compound	XpdTTD,allele
R3283	T4915	T4895	punct	.,rescued
R3284	T4917	T4918	mark	Because,rescued
R3285	T4918	T4924	advcl	rescued,considered
R3286	T4919	T4920	amod	embryonic,lethality
R3287	T4920	T4918	nsubjpass	lethality,rescued
R3288	T4921	T4918	auxpass	was,rescued
R3289	T4922	T4918	advmod	also,rescued
R329	T653	T654	punct	[,3
R3290	T4923	T4918	advmod	fully,rescued
R3291	T4925	T4918	prep	in,rescued
R3292	T4926	T4927	nmod	XpdTTD,KO
R3293	T4927	T4929	nmod	KO,mice
R3294	T4928	T4927	punct	/,KO
R3295	T4929	T4925	pobj	mice,in
R3296	T4930	T4929	amod	hemizygous,mice
R3297	T4931	T4924	punct	", ",considered
R3298	T4932	T4933	det	the,allele
R3299	T4933	T4924	nsubjpass	allele,considered
R33	T120	T114	punct	", ",documented
R330	T654	T652	parataxis	3,lyase
R3300	T4934	T4933	compound	XpdTTD,allele
R3301	T4935	T4924	aux	can,considered
R3302	T4936	T4924	auxpass	be,considered
R3303	T4937	T4924	prep	as,considered
R3304	T4938	T4937	pobj	wt,as
R3305	T4939	T4938	cc	and,wt
R3306	T4940	T4941	advmod	thus,dominant
R3307	T4941	T4938	conj	dominant,wt
R3308	T4942	T4941	prep	to,dominant
R3309	T4943	T4942	pobj	each,to
R331	T655	T654	punct	],3
R3310	T4944	T4943	prep	of,each
R3311	T4945	T4946	det	the,alleles
R3312	T4946	T4944	pobj	alleles,of
R3313	T4947	T4946	amod	homozygous,alleles
R3314	T4948	T4946	amod	lethal,alleles
R3315	T4949	T4950	punct	(,XpdKO
R3316	T4950	T4946	parataxis	XpdKO,alleles
R3317	T4951	T4950	punct	", ",XpdKO
R3318	T4952	T4950	conj	Xpd†XPCS,XpdKO
R3319	T4953	T4952	punct	", ",Xpd†XPCS
R332	T656	T652	punct	", ",lyase
R3320	T4954	T4952	cc	and,Xpd†XPCS
R3321	T4955	T4952	conj	Xpd†XP,Xpd†XPCS
R3322	T4956	T4950	punct	),XpdKO
R3323	T4957	T4941	prep	with,dominant
R3324	T4958	T4957	pobj	respect,with
R3325	T4959	T4958	prep	to,respect
R3326	T4960	T4961	det	this,phenotype
R3327	T4961	T4959	pobj	phenotype,to
R3328	T4962	T4961	amod	particular,phenotype
R3329	T4963	T4964	punct	(,Table
R333	T657	T658	nmod	galactose,phosphate
R3330	T4964	T4924	parataxis	Table,considered
R3331	T4965	T4964	nummod	2,Table
R3332	T4966	T4964	punct	),Table
R3333	T4967	T4924	punct	.,considered
R3334	T4969	T4970	npadvmod	TTD,specific
R3335	T4970	T4972	amod	specific,features
R3336	T4971	T4970	punct	-,specific
R3337	T4972	T4976	nsubjpass	features,thought
R3338	T4973	T4972	amod	cutaneous,features
R3339	T4974	T4973	cc	and,cutaneous
R334	T658	T662	compound	phosphate,uridylyltransferase
R3340	T4975	T4973	conj	anaemic,cutaneous
R3341	T4977	T4976	punct	", ",thought
R3342	T4978	T4976	prep	on,thought
R3343	T4979	T4980	det	the,hand
R3344	T4980	T4978	pobj	hand,on
R3345	T4981	T4980	amod	other,hand
R3346	T4982	T4976	punct	", ",thought
R3347	T4983	T4976	auxpass	are,thought
R3348	T4984	T4985	aux	to,result
R3349	T4985	T4976	xcomp	result,thought
R335	T659	T658	punct	-,phosphate
R3350	T4986	T4985	prep	from,result
R3351	T4987	T4988	det	a,kind
R3352	T4988	T4986	pobj	kind,from
R3353	T4989	T4988	amod	specific,kind
R3354	T4990	T4988	prep	of,kind
R3355	T4991	T4992	amod	transcriptional,insufficiency
R3356	T4992	T4990	pobj	insufficiency,of
R3357	T4993	T4988	acl	caused,kind
R3358	T4994	T4993	agent	by,caused
R3359	T4995	T4994	pobj	depletion,by
R336	T660	T658	nummod	1,phosphate
R3360	T4996	T4995	prep	of,depletion
R3361	T4997	T4998	amod	unstable,TFIIH
R3362	T4998	T4996	pobj	TFIIH,of
R3363	T4999	T4995	prep	during,depletion
R3364	T5000	T5001	det	the,differentiation
R3365	T5001	T4999	pobj	differentiation,during
R3366	T5002	T5001	amod	terminal,differentiation
R3367	T5003	T5001	prep	of,differentiation
R3368	T5004	T5005	nmod	skin,cells
R3369	T5005	T5003	pobj	cells,of
R337	T661	T658	punct	-,phosphate
R3370	T5006	T5004	punct	", ",skin
R3371	T5007	T5008	compound	hair,shaft
R3372	T5008	T5004	conj	shaft,skin
R3373	T5009	T5008	punct	-,shaft
R3374	T5010	T5008	punct	", ",shaft
R3375	T5011	T5008	cc	and,shaft
R3376	T5012	T5008	conj	blood,shaft
R3377	T5013	T5014	punct	[,24
R3378	T5014	T4976	parataxis	24,thought
R3379	T5015	T5014	nummod	16,24
R338	T662	T652	conj	uridylyltransferase,lyase
R3380	T5016	T5014	punct	",",24
R3381	T5017	T5014	punct	],24
R3382	T5018	T4976	punct	.,thought
R3383	T5020	T5021	prep	In,were
R3384	T5022	T5023	nmod	compound,mice
R3385	T5023	T5020	pobj	mice,In
R3386	T5024	T5023	amod	heterozygous,mice
R3387	T5025	T5021	punct	", ",were
R3388	T5026	T5027	det	both,alleles
R3389	T5027	T5021	nsubj	alleles,were
R339	T663	T664	punct	[,4
R3390	T5028	T5027	amod	homozygous,alleles
R3391	T5029	T5027	amod	lethal,alleles
R3392	T5030	T5027	nmod	Xpd†XPCS,alleles
R3393	T5031	T5030	cc	and,Xpd†XPCS
R3394	T5032	T5030	conj	Xpd†XP,Xpd†XPCS
R3395	T5033	T5021	acomp	able,were
R3396	T5034	T5035	aux	to,alleviate
R3397	T5035	T5033	xcomp	alleviate,able
R3398	T5036	T5037	npadvmod	XpdTTD,specific
R3399	T5037	T5039	amod	specific,features
R34	T121	T122	poss	its,potential
R340	T664	T662	parataxis	4,uridylyltransferase
R3400	T5038	T5037	punct	-,specific
R3401	T5039	T5035	dobj	features,alleviate
R3402	T5040	T5039	amod	cutaneous,features
R3403	T5041	T5040	cc	and,cutaneous
R3404	T5042	T5040	conj	anaemic,cutaneous
R3405	T5043	T5021	cc	and,were
R3406	T5044	T5045	aux	can,defined
R3407	T5045	T5021	conj	defined,were
R3408	T5046	T5045	advmod	thus,defined
R3409	T5047	T5045	auxpass	be,defined
R341	T665	T664	punct	],4
R3410	T5048	T5045	prep	as,defined
R3411	T5049	T5048	amod	dominant,as
R3412	T5050	T5045	prep	over,defined
R3413	T5051	T5052	det	the,allele
R3414	T5052	T5050	pobj	allele,over
R3415	T5053	T5052	compound	XpdTTD,allele
R3416	T5054	T5045	prep	with,defined
R3417	T5055	T5054	pobj	respect,with
R3418	T5056	T5055	prep	to,respect
R3419	T5057	T5058	det	these,phenotypes
R342	T666	T662	punct	", ",uridylyltransferase
R3420	T5058	T5056	pobj	phenotypes,to
R3421	T5059	T5021	punct	.,were
R3422	T5061	T5062	nsubj	We,conclude
R3423	T5063	T5064	mark	that,represent
R3424	T5064	T5062	ccomp	represent,conclude
R3425	T5065	T5066	det	the,defects
R3426	T5066	T5064	nsubj	defects,represent
R3427	T5067	T5066	acl	leading,defects
R3428	T5068	T5067	prep	to,leading
R3429	T5069	T5070	amod	embryonic,lethality
R343	T667	T662	cc	and,uridylyltransferase
R3430	T5070	T5068	pobj	lethality,to
R3431	T5071	T5070	cc	and,lethality
R3432	T5072	T5073	amod	aberrant,differentiation
R3433	T5073	T5070	conj	differentiation,lethality
R3434	T5074	T5073	amod	terminal,differentiation
R3435	T5075	T5073	prep	of,differentiation
R3436	T5076	T5077	det	the,skin
R3437	T5077	T5075	pobj	skin,of
R3438	T5078	T5077	punct	", ",skin
R3439	T5079	T5077	conj	hair,skin
R344	T668	T669	compound	methylmalonyl,mutase
R3440	T5080	T5079	punct	", ",hair
R3441	T5081	T5079	cc	and,hair
R3442	T5082	T5079	conj	blood,hair
R3443	T5083	T5084	nummod	two,deficiencies
R3444	T5084	T5064	dobj	deficiencies,represent
R3445	T5085	T5086	advmod	qualitatively,different
R3446	T5086	T5084	amod	different,deficiencies
R3447	T5087	T5085	cc	and,qualitatively
R3448	T5088	T5087	punct	/,and
R3449	T5089	T5087	cc	or,and
R345	T669	T662	conj	mutase,uridylyltransferase
R3450	T5090	T5085	conj	quantitatively,qualitatively
R3451	T5091	T5084	amod	transcriptional,deficiencies
R3452	T5092	T5062	punct	.,conclude
R3453	T5094	T5095	prep	During,is
R3454	T5096	T5097	amod	early,development
R3455	T5097	T5094	pobj	development,During
R3456	T5098	T5097	amod	embryonic,development
R3457	T5099	T5095	punct	", ",is
R3458	T5100	T5095	nsubj	XpdTTD,is
R3459	T5101	T5095	acomp	dominant,is
R346	T670	T669	compound	CoA,mutase
R3460	T5102	T5101	prep	over,dominant
R3461	T5103	T5104	det	the,alleles
R3462	T5104	T5102	pobj	alleles,over
R3463	T5105	T5104	nmod	Xpd†XPCS,alleles
R3464	T5106	T5105	cc	and,Xpd†XPCS
R3465	T5107	T5105	conj	Xpd†XP,Xpd†XPCS
R3466	T5108	T5095	punct	", ",is
R3467	T5109	T5110	mark	whereas,reversed
R3468	T5110	T5095	advcl	reversed,is
R3469	T5111	T5110	advmod	later,reversed
R347	T671	T672	punct	[,5
R3470	T5112	T5111	prep	in,later
R3471	T5113	T5114	det	the,ontogenesis
R3472	T5114	T5112	pobj	ontogenesis,in
R3473	T5115	T5114	prep	of,ontogenesis
R3474	T5116	T5115	pobj	skin,of
R3475	T5117	T5116	punct	", ",skin
R3476	T5118	T5119	compound	hair,shaft
R3477	T5119	T5116	conj	shaft,skin
R3478	T5120	T5119	punct	-,shaft
R3479	T5121	T5119	punct	", ",shaft
R348	T672	T669	parataxis	5,mutase
R3480	T5122	T5119	cc	and,shaft
R3481	T5123	T5124	compound	blood,cells
R3482	T5124	T5119	conj	cells,shaft
R3483	T5125	T5110	punct	", ",reversed
R3484	T5126	T5127	det	the,situation
R3485	T5127	T5110	nsubjpass	situation,reversed
R3486	T5128	T5110	auxpass	is,reversed
R3487	T5129	T5095	punct	.,is
R3488	T5131	T5132	prep	In,imparted
R3489	T5133	T5134	poss	its,role
R349	T673	T672	punct	],5
R3490	T5134	T5131	pobj	role,In
R3491	T5135	T5134	prep	in,role
R3492	T5136	T5137	det	the,repair
R3493	T5137	T5135	pobj	repair,in
R3494	T5138	T5137	prep	of,repair
R3495	T5139	T5140	compound	UV,photolesions
R3496	T5140	T5138	pobj	photolesions,of
R3497	T5141	T5132	punct	", ",imparted
R3498	T5142	T5143	det	the,allele
R3499	T5143	T5132	nsubj	allele,imparted
R35	T122	T114	nsubjpass	potential,documented
R350	T674	T616	punct	.,limited
R3500	T5144	T5143	compound	Xpd†XPCS,allele
R3501	T5145	T5146	det	a,benefit
R3502	T5146	T5132	dobj	benefit,imparted
R3503	T5147	T5146	amod	clear,benefit
R3504	T5148	T5146	compound	UV,benefit
R3505	T5149	T5146	compound	survival,benefit
R3506	T5150	T5146	prep	over,benefit
R3507	T5151	T5152	det	a,allele
R3508	T5152	T5150	pobj	allele,over
R3509	T5153	T5152	amod	single,allele
R351	T676	T677	amod	Compound,heterozygotes
R3510	T5154	T5152	compound	XpdTTD,allele
R3511	T5155	T5152	cc	or,allele
R3512	T5156	T5157	nummod	two,alleles
R3513	T5157	T5152	conj	alleles,allele
R3514	T5158	T5157	compound	XpdXPCS,alleles
R3515	T5159	T5146	amod	independent,benefit
R3516	T5160	T5159	prep	of,independent
R3517	T5161	T5162	compound	expression,levels
R3518	T5162	T5160	pobj	levels,of
R3519	T5163	T5132	punct	", ",imparted
R352	T677	T678	nsubj	heterozygotes,are
R3520	T5164	T5165	dep	which,is
R3521	T5165	T5132	advcl	is,imparted
R3522	T5166	T5165	acomp	consistent,is
R3523	T5167	T5166	prep	with,consistent
R3524	T5168	T5169	amod	interallelic,complementation
R3525	T5169	T5167	pobj	complementation,with
R3526	T5170	T5132	punct	.,imparted
R3527	T5172	T5173	advmod	However,argues
R3528	T5174	T5173	punct	", ",argues
R3529	T5175	T5176	det	the,observation
R353	T679	T678	attr	individuals,are
R3530	T5176	T5173	nsubj	observation,argues
R3531	T5177	T5178	mark	that,improved
R3532	T5178	T5176	acl	improved,observation
R3533	T5179	T5180	det	no,parameters
R3534	T5180	T5178	nsubjpass	parameters,improved
R3535	T5181	T5180	amod	other,parameters
R3536	T5182	T5180	amod	cellular,parameters
R3537	T5183	T5182	cc	or,cellular
R3538	T5184	T5182	conj	biochemical,cellular
R3539	T5185	T5186	npadvmod	UV,related
R354	T680	T679	acl	carrying,individuals
R3540	T5186	T5180	amod	related,parameters
R3541	T5187	T5186	punct	-,related
R3542	T5188	T5178	auxpass	were,improved
R3543	T5189	T5178	prep	in,improved
R3544	T5190	T5191	compound	XpdTTD, †XPCS
R3545	T5191	T5189	pobj	†XPCS,in
R3546	T5192	T5191	punct	/, †XPCS
R3547	T5193	T5173	prep	against,argues
R3548	T5194	T5193	pobj	complementation,against
R3549	T5195	T5194	prep	of,complementation
R355	T681	T682	nummod	two,alleles
R3550	T5196	T5197	det	this,activity
R3551	T5197	T5195	pobj	activity,of
R3552	T5198	T5197	compound	repair,activity
R3553	T5199	T5194	prep	in,complementation
R3554	T5200	T5201	det	the,rescue
R3555	T5201	T5199	pobj	rescue,in
R3556	T5202	T5201	prep	of,rescue
R3557	T5203	T5204	nmod	TTD,symptoms
R3558	T5204	T5202	pobj	symptoms,of
R3559	T5205	T5204	amod	progeroid,symptoms
R356	T682	T680	dobj	alleles,carrying
R3560	T5206	T5207	advmod	in,vivo
R3561	T5207	T5201	advmod	vivo,rescue
R3562	T5208	T5173	punct	.,argues
R3565	T5295	T5296	amod	Interallelic,Complementation
R3566	T5297	T5296	cc	and,Complementation
R3567	T5298	T5299	compound	XPD,Function
R3568	T5299	T5296	conj	Function,Complementation
R3569	T5301	T5302	dep	What,tell
R357	T683	T682	amod	different,alleles
R3570	T5303	T5302	aux	does,tell
R3571	T5304	T5305	amod	interallelic,complementation
R3572	T5305	T5302	nsubj	complementation,tell
R3573	T5306	T5302	dobj	us,tell
R3574	T5307	T5302	prep	about,tell
R3575	T5308	T5309	det	the,mechanism
R3576	T5309	T5307	pobj	mechanism,about
R3577	T5310	T5309	prep	of,mechanism
R3578	T5311	T5312	compound	XPD,function
R3579	T5312	T5310	pobj	function,of
R358	T684	T682	amod	mutant,alleles
R3580	T5313	T5302	punct	?,tell
R3581	T5315	T5316	amod	Interallelic,complementation
R3582	T5316	T5317	nsubjpass	complementation,observed
R3583	T5318	T5317	auxpass	is,observed
R3584	T5319	T5320	advmod	most,often
R3585	T5320	T5317	advmod	often,observed
R3586	T5321	T5317	prep	in,observed
R3587	T5322	T5323	amod	multimeric,proteins
R3588	T5323	T5321	pobj	proteins,in
R3589	T5324	T5323	prep	with,proteins
R359	T685	T682	prep	of,alleles
R3590	T5325	T5326	amod	multiple,domains
R3591	T5326	T5324	pobj	domains,with
R3592	T5327	T5326	amod	functional,domains
R3593	T5328	T5317	punct	.,observed
R3594	T5330	T5331	advmod	Unfortunately,remains
R3595	T5332	T5331	punct	", ",remains
R3596	T5333	T5334	det	the,relationship
R3597	T5334	T5331	nsubj	relationship,remains
R3598	T5335	T5336	compound	structure,function
R3599	T5336	T5334	compound	function,relationship
R36	T123	T124	aux	to,impact
R360	T686	T687	det	the,gene
R3600	T5337	T5336	punct	–,function
R3601	T5338	T5334	prep	between,relationship
R3602	T5339	T5340	npadvmod	disease,causing
R3603	T5340	T5342	amod	causing,mutations
R3604	T5341	T5340	punct	-,causing
R3605	T5342	T5338	pobj	mutations,between
R3606	T5343	T5342	cc	and,mutations
R3607	T5344	T5345	nmod	XPD,domains
R3608	T5345	T5342	conj	domains,mutations
R3609	T5346	T5345	amod	functional,domains
R361	T687	T685	pobj	gene,of
R3610	T5347	T5334	punct	", ",relationship
R3611	T5348	T5334	prep	including,relationship
R3612	T5349	T5350	amod	detailed,information
R3613	T5350	T5348	pobj	information,including
R3614	T5351	T5350	amod	structural,information
R3615	T5352	T5350	prep	on,information
R3616	T5353	T5352	pobj	XPD,on
R3617	T5354	T5353	cc	or,XPD
R3618	T5355	T5356	advmod	even,stoichiometry
R3619	T5356	T5353	conj	stoichiometry,XPD
R362	T688	T687	amod	same,gene
R3620	T5357	T5356	poss	its,stoichiometry
R3621	T5358	T5350	prep	within,information
R3622	T5359	T5358	pobj	TFIIH,within
R3623	T5360	T5331	punct	", ",remains
R3624	T5361	T5331	acomp	unknown,remains
R3625	T5362	T5331	punct	.,remains
R3626	T5364	T5365	advmod	However,is
R3627	T5366	T5365	punct	", ",is
R3628	T5367	T5365	prep	based,is
R3629	T5368	T5367	prep	on,based
R363	T689	T678	punct	.,are
R3630	T5369	T5370	det	the,ability
R3631	T5370	T5368	pobj	ability,on
R3632	T5371	T5370	prep	of,ability
R3633	T5372	T5373	compound	cell,extracts
R3634	T5373	T5371	pobj	extracts,of
R3635	T5374	T5375	dep	that,are
R3636	T5375	T5373	relcl	are,extracts
R3637	T5376	T5375	acomp	defective,are
R3638	T5377	T5376	prep	in,defective
R3639	T5378	T5379	nummod	two,components
R364	T691	T692	prep	In,result
R3640	T5379	T5377	pobj	components,in
R3641	T5380	T5379	amod	different,components
R3642	T5381	T5379	compound	TFIIH,components
R3643	T5382	T5379	punct	(,components
R3644	T5383	T5379	appos	XPD,components
R3645	T5384	T5383	cc	and,XPD
R3646	T5385	T5383	conj	XPB,XPD
R3647	T5386	T5370	punct	),ability
R3648	T5387	T5388	aux	to,complement
R3649	T5388	T5370	acl	complement,ability
R365	T693	T694	det	the,absence
R3650	T5389	T5390	compound	NER,activity
R3651	T5390	T5388	dobj	activity,complement
R3652	T5391	T5392	advmod	in,vitro
R3653	T5392	T5388	advmod	vitro,complement
R3654	T5393	T5394	punct	[,26
R3655	T5394	T5370	parataxis	26,ability
R3656	T5395	T5394	punct	],26
R3657	T5396	T5365	punct	", ",is
R3658	T5397	T5365	nsubj	it,is
R3659	T5398	T5365	acomp	likely,is
R366	T694	T691	pobj	absence,In
R3660	T5399	T5400	mark	that,multimerise
R3661	T5400	T5365	ccomp	multimerise,is
R3662	T5401	T5400	nsubj	TFIIH,multimerise
R3663	T5402	T5401	punct	(,TFIIH
R3664	T5403	T5401	cc	or,TFIIH
R3665	T5404	T5405	poss	its,components
R3666	T5405	T5401	conj	components,TFIIH
R3667	T5406	T5400	punct	),multimerise
R3668	T5407	T5400	aux	can,multimerise
R3669	T5408	T5400	preconj	either,multimerise
R367	T695	T694	prep	of,absence
R3670	T5409	T5400	cc	or,multimerise
R3671	T5410	T5400	conj	exchange,multimerise
R3672	T5411	T5412	advmod	at,least
R3673	T5412	T5413	advmod	least,during
R3674	T5413	T5410	prep	during,exchange
R3675	T5414	T5415	det	the,reaction
R3676	T5415	T5413	pobj	reaction,during
R3677	T5416	T5415	compound	NER,reaction
R3678	T5417	T5365	punct	.,is
R3679	T5419	T5420	advmod	Furthermore,known
R368	T696	T697	det	a,allele
R3680	T5421	T5420	punct	", ",known
R3681	T5422	T5420	nsubjpass	XPD,known
R3682	T5423	T5420	auxpass	is,known
R3683	T5424	T5425	aux	to,be
R3684	T5425	T5420	xcomp	be,known
R3685	T5426	T5427	det	a,subunit
R3686	T5427	T5425	attr	subunit,be
R3687	T5428	T5427	advmod	“,subunit
R3688	T5429	T5430	advmod	loosely,bound
R3689	T5430	T5427	amod	bound,subunit
R369	T697	T695	pobj	allele,of
R3690	T5431	T5427	punct	”,subunit
R3691	T5432	T5427	prep	of,subunit
R3692	T5433	T5432	pobj	TFIIH,of
R3693	T5434	T5435	punct	[,27
R3694	T5435	T5420	parataxis	27,known
R3695	T5436	T5435	punct	],27
R3696	T5437	T5420	punct	.,known
R3697	T5439	T5440	nsubj	We,envisage
R3698	T5441	T5440	advmod	thus,envisage
R3699	T5442	T5443	det	the,mechanism
R37	T124	T122	acl	impact,potential
R370	T698	T697	amod	dominant,allele
R3700	T5443	T5445	nsubj	mechanism,involve
R3701	T5444	T5443	amod	molecular,mechanism
R3702	T5445	T5440	ccomp	involve,envisage
R3703	T5446	T5443	prep	of,mechanism
R3704	T5447	T5448	amod	interallelic,complementation
R3705	T5448	T5446	pobj	complementation,of
R3706	T5449	T5445	aux	to,involve
R3707	T5450	T5451	det	the,exchange
R3708	T5451	T5445	dobj	exchange,involve
R3709	T5452	T5451	prep	of,exchange
R371	T699	T697	punct	(,allele
R3710	T5453	T5454	compound	XPD,molecules
R3711	T5454	T5452	pobj	molecules,of
R3712	T5455	T5451	prep	within,exchange
R3713	T5456	T5457	det	the,complex
R3714	T5457	T5455	pobj	complex,within
R3715	T5458	T5457	compound	TFIIH,complex
R3716	T5459	T5451	cc	or,exchange
R3717	T5460	T5451	conj	turnover,exchange
R3718	T5461	T5460	prep	of,turnover
R3719	T5462	T5463	compound	TFIIH,complexes
R372	T700	T701	amod	wild,type
R3720	T5463	T5461	pobj	complexes,of
R3721	T5464	T5463	acl	containing,complexes
R3722	T5465	T5466	amod	different,molecules
R3723	T5466	T5464	dobj	molecules,containing
R3724	T5467	T5466	compound	XPD,molecules
R3725	T5468	T5460	prep	at,turnover
R3726	T5469	T5470	det	the,site
R3727	T5470	T5468	pobj	site,at
R3728	T5471	T5470	prep	of,site
R3729	T5472	T5473	compound	DNA,damage
R373	T701	T697	nmod	type,allele
R3730	T5473	T5471	pobj	damage,of
R3731	T5474	T5460	prep	during,turnover
R3732	T5475	T5476	det	the,course
R3733	T5476	T5474	pobj	course,during
R3734	T5477	T5476	prep	of,course
R3735	T5478	T5479	det	the,genome
R3736	T5479	T5477	pobj	genome,of
R3737	T5480	T5479	amod	global,genome
R3738	T5481	T5482	advmod	as,as
R3739	T5482	T5451	cc	as,exchange
R374	T702	T701	punct	-,type
R3740	T5483	T5482	advmod	well,as
R3741	T5484	T5485	npadvmod	transcription,coupled
R3742	T5485	T5487	amod	coupled,repair
R3743	T5486	T5485	punct	-,coupled
R3744	T5487	T5451	conj	repair,exchange
R3745	T5488	T5487	prep	of,repair
R3746	T5489	T5490	preconj	either,damage
R3747	T5490	T5488	pobj	damage,of
R3748	T5491	T5492	npadvmod	UV,induced
R3749	T5492	T5490	amod	induced,damage
R375	T703	T701	punct	[,type
R3750	T5493	T5492	punct	-,induced
R3751	T5494	T5492	cc	or,induced
R3752	T5495	T5492	conj	endogenous,induced
R3753	T5496	T5490	compound	DNA,damage
R3754	T5497	T5440	punct	.,envisage
R3755	T5607	T5608	det	A,Paradigm
R3756	T5609	T5608	amod	Biallelic,Paradigm
R3757	T5610	T5608	prep	for,Paradigm
R3758	T5611	T5612	compound	XPD,Disorders
R3759	T5612	T5610	pobj	Disorders,for
R376	T704	T701	appos	wt,type
R3760	T5614	T5615	advmod	Recently,characterised
R3761	T5616	T5615	punct	", ",characterised
R3762	T5617	T5615	nsubjpass	proteins,characterised
R3763	T5618	T5617	acl	originating,proteins
R3764	T5619	T5618	prep	from,originating
R3765	T5620	T5621	amod	presumed,alleles
R3766	T5621	T5619	pobj	alleles,from
R3767	T5622	T5621	amod	null,alleles
R3768	T5623	T5615	auxpass	were,characterised
R3769	T5624	T5615	advmod	biochemically,characterised
R377	T705	T697	punct	],allele
R3770	T5625	T5615	prep	as,characterised
R3771	T5626	T5625	amod	inactive,as
R3772	T5627	T5615	prep	in,characterised
R3773	T5628	T5629	amod	basal,transcription
R3774	T5629	T5627	pobj	transcription,in
R3775	T5630	T5631	punct	[,27
R3776	T5631	T5615	parataxis	27,characterised
R3777	T5632	T5631	punct	],27
R3778	T5633	T5615	punct	", ",characterised
R3779	T5634	T5615	advcl	providing,characterised
R378	T706	T697	punct	),allele
R3780	T5635	T5636	det	an,explanation
R3781	T5636	T5634	dobj	explanation,providing
R3782	T5637	T5636	prep	as,explanation
R3783	T5638	T5637	prep	to,as
R3784	T5639	T5640	advmod	why,failed
R3785	T5640	T5638	pcomp	failed,to
R3786	T5641	T5642	det	these,alleles
R3787	T5642	T5640	nsubj	alleles,failed
R3788	T5643	T5644	aux	to,rescue
R3789	T5644	T5640	xcomp	rescue,failed
R379	T707	T692	punct	", ",result
R3790	T5645	T5644	dobj	lethality,rescue
R3791	T5646	T5644	prep	in,rescue
R3792	T5647	T5648	amod	haploid,pombe
R3793	T5648	T5646	pobj	pombe,in
R3794	T5649	T5648	nmod	S.,pombe
R3795	T5650	T5648	prep	with,pombe
R3796	T5651	T5652	det	a,mutation
R3797	T5652	T5650	pobj	mutation,with
R3798	T5653	T5652	amod	null,mutation
R3799	T5654	T5652	prep	in,mutation
R38	T125	T126	compound	disease,outcome
R380	T708	T709	amod	genetic,interactions
R3800	T5655	T5656	det	the,homologue
R3801	T5656	T5654	pobj	homologue,in
R3802	T5657	T5656	compound	XPD,homologue
R3803	T5658	T5656	appos	rad15,homologue
R3804	T5659	T5660	punct	[,19
R3805	T5660	T5640	parataxis	19,failed
R3806	T5661	T5660	punct	],19
R3807	T5662	T5615	punct	.,characterised
R3808	T5664	T5665	poss	Our,data
R3809	T5665	T5666	nsubj	data,suggest
R381	T709	T692	nsubj	interactions,result
R3810	T5667	T5668	mark	that,have
R3811	T5668	T5666	ccomp	have,suggest
R3812	T5669	T5670	amod	certain,alleles
R3813	T5670	T5668	nsubj	alleles,have
R3814	T5671	T5672	advmod	presumed,null
R3815	T5672	T5670	amod	null,alleles
R3816	T5673	T5668	punct	", ",have
R3817	T5674	T5675	mark	although,unable
R3818	T5675	T5668	advcl	unable,have
R3819	T5676	T5677	prep	on,support
R382	T710	T709	prep	between,interactions
R3820	T5677	T5675	xcomp	support,unable
R3821	T5678	T5679	poss	their,own
R3822	T5679	T5676	pobj	own,on
R3823	T5680	T5677	aux	to,support
R3824	T5681	T5682	amod	basal,transcription
R3825	T5682	T5677	dobj	transcription,support
R3826	T5683	T5668	punct	", ",have
R3827	T5684	T5668	aux	may,have
R3828	T5685	T5668	prep	in,have
R3829	T5686	T5685	pobj	fact,in
R383	T711	T712	amod	recessive,alleles
R3830	T5687	T5688	det	a,impact
R3831	T5688	T5668	dobj	impact,have
R3832	T5689	T5688	amod	substantial,impact
R3833	T5690	T5688	prep	on,impact
R3834	T5691	T5692	compound	disease,outcome
R3835	T5692	T5690	pobj	outcome,on
R3836	T5693	T5688	prep	in,impact
R3837	T5694	T5695	nmod	compound,humans
R3838	T5695	T5693	pobj	humans,in
R3839	T5696	T5695	amod	heterozygous,humans
R384	T712	T710	pobj	alleles,between
R3840	T5697	T5668	punct	", ",have
R3841	T5698	T5699	mark	as,in
R3842	T5699	T5668	advcl	in,have
R3843	T5700	T5699	nsubj	they,in
R3844	T5701	T5699	aux	do,in
R3845	T5702	T5703	compound	mouse,models
R3846	T5703	T5699	pobj	models,in
R3847	T5704	T5666	punct	.,suggest
R3848	T5706	T5707	amod	Clinical,evidence
R3849	T5707	T5708	nsubj	evidence,comes
R385	T713	T709	punct	(,interactions
R3850	T5709	T5707	prep	in,evidence
R3851	T5710	T5709	pobj	support,in
R3852	T5711	T5710	prep	of,support
R3853	T5712	T5713	det	this,hypothesis
R3854	T5713	T5711	pobj	hypothesis,of
R3855	T5714	T5708	prep	from,comes
R3856	T5715	T5716	det	a,number
R3857	T5716	T5714	pobj	number,from
R3858	T5717	T5716	prep	of,number
R3859	T5718	T5719	compound	XP,patients
R386	T714	T709	acl	referred,interactions
R3860	T5719	T5717	pobj	patients,of
R3861	T5720	T5719	compound	complementation,patients
R3862	T5721	T5722	compound	group,D
R3863	T5722	T5719	compound	D,patients
R3864	T5723	T5724	dep	that,fit
R3865	T5724	T5719	relcl	fit,patients
R3866	T5725	T5724	aux	do,fit
R3867	T5726	T5724	neg	not,fit
R3868	T5727	T5724	prep	within,fit
R3869	T5728	T5729	det	the,framework
R387	T715	T714	prep	to,referred
R3870	T5729	T5727	pobj	framework,within
R3871	T5730	T5729	prep	of,framework
R3872	T5731	T5732	det	the,paradigm
R3873	T5732	T5730	pobj	paradigm,of
R3874	T5733	T5732	amod	current,paradigm
R3875	T5734	T5732	amod	monoallelic,paradigm
R3876	T5735	T5732	prep	of,paradigm
R3877	T5736	T5737	compound	XPD,disorders
R3878	T5737	T5735	pobj	disorders,of
R3879	T5738	T5739	punct	(,Figure
R388	T716	T714	advmod	here,referred
R3880	T5739	T5708	parataxis	Figure,comes
R3881	T5740	T5739	nummod	5,Figure
R3882	T5741	T5739	punct	),Figure
R3883	T5742	T5708	punct	.,comes
R3884	T5744	T5745	prep	In,had
R3885	T5746	T5744	pobj	contrast,In
R3886	T5747	T5746	prep	to,contrast
R3887	T5748	T5749	nummod	two,patients
R3888	T5749	T5747	pobj	patients,to
R3889	T5750	T5749	amod	hemizygous,patients
R389	T717	T714	prep	as,referred
R3890	T5751	T5749	compound	XPDXPCS,patients
R3891	T5752	T5749	acl	carrying,patients
R3892	T5753	T5754	det	the,alleles
R3893	T5754	T5752	dobj	alleles,carrying
R3894	T5755	T5756	npadvmod	XPDG47R,encoding
R3895	T5756	T5754	amod	encoding,alleles
R3896	T5757	T5755	punct	-,XPDG47R
R3897	T5758	T5755	cc	or,XPDG47R
R3898	T5759	T5755	conj	XPDR666W,XPDG47R
R3899	T5760	T5756	punct	-,encoding
R39	T126	T124	dobj	outcome,impact
R390	T718	T717	punct	“,as
R3900	T5761	T5762	dep	who,died
R3901	T5762	T5754	relcl	died,alleles
R3902	T5763	T5762	prep	of,died
R3903	T5764	T5765	det	the,disease
R3904	T5765	T5763	pobj	disease,of
R3905	T5766	T5762	prep	before,died
R3906	T5767	T5768	nummod	2,y
R3907	T5768	T5766	pobj	y,before
R3908	T5769	T5768	prep	of,y
R3909	T5770	T5769	pobj	age,of
R391	T719	T720	amod	biallelic,effects
R3910	T5771	T5745	punct	", ",had
R3911	T5772	T5773	nummod	two,patients
R3912	T5773	T5745	nsubj	patients,had
R3913	T5774	T5773	amod	compound,patients
R3914	T5775	T5773	amod	heterozygous,patients
R3915	T5776	T5773	compound	XPDXPCS,patients
R3916	T5777	T5773	acl	carrying,patients
R3917	T5778	T5779	det	the,alleles
R3918	T5779	T5777	dobj	alleles,carrying
R3919	T5780	T5779	amod	same,alleles
R392	T720	T717	pobj	effects,as
R3920	T5781	T5782	npadvmod	XPDG47R,encoding
R3921	T5782	T5779	amod	encoding,alleles
R3922	T5783	T5781	punct	-,XPDG47R
R3923	T5784	T5781	cc	or,XPDG47R
R3924	T5785	T5781	conj	XPDR666W,XPDG47R
R3925	T5786	T5782	punct	-,encoding
R3926	T5787	T5779	prep	in,alleles
R3927	T5788	T5787	pobj	addition,in
R3928	T5789	T5788	prep	to,addition
R3929	T5790	T5791	det	the,730
R393	T721	T720	punct	”,effects
R3930	T5791	T5789	pobj	730,to
R3931	T5792	T5793	advmod	presumed,null
R3932	T5793	T5791	amod	null,730
R3933	T5794	T5791	nmod	XPDL461V,730
R3934	T5795	T5791	punct	+,730
R3935	T5796	T5791	compound	del716,730
R3936	T5797	T5791	punct	−,730
R3937	T5798	T5773	appos	both,patients
R3938	T5799	T5800	advmod	considerably,milder
R3939	T5800	T5801	amod	milder,symptoms
R394	T722	T692	punct	),result
R3940	T5801	T5745	dobj	symptoms,had
R3941	T5802	T5801	compound	disease,symptoms
R3942	T5803	T5745	cc	and,had
R3943	T5804	T5745	conj	survived,had
R3944	T5805	T5806	amod	more,ten
R3945	T5806	T5808	nummod	ten,times
R3946	T5807	T5806	quantmod	than,ten
R3947	T5808	T5809	npadvmod	times,longer
R3948	T5809	T5804	advmod	longer,survived
R3949	T5810	T5811	punct	(,A.
R395	T723	T692	aux	could,result
R3950	T5811	T5804	meta	A.,survived
R3951	T5812	T5811	nmod	Lehmann,A.
R3952	T5813	T5811	punct	", ",A.
R3953	T5814	T5811	amod	personal,A.
R3954	T5815	T5811	nmod	communication,A.
R3955	T5816	T5811	punct	),A.
R3956	T5817	T5818	punct	(,Figure
R3957	T5818	T5804	parataxis	Figure,survived
R3958	T5819	T5818	nummod	5,Figure
R3959	T5820	T5818	punct	),Figure
R396	T724	T692	prep	in,result
R3960	T5821	T5745	punct	.,had
R3961	T5823	T5824	compound	Compound,heterozygosity
R3962	T5824	T5825	nsubjpass	heterozygosity,associated
R3963	T5826	T5825	auxpass	is,associated
R3964	T5827	T5825	advmod	also,associated
R3965	T5828	T5825	prep	with,associated
R3966	T5829	T5830	det	the,syndrome
R3967	T5830	T5828	pobj	syndrome,with
R3968	T5831	T5832	advmod	recently,reported
R3969	T5832	T5830	amod	reported,syndrome
R397	T725	T726	amod	different,outcomes
R3970	T5833	T5830	nmod	combination,syndrome
R3971	T5834	T5830	nmod	XP,syndrome
R3972	T5835	T5834	cc	and,XP
R3973	T5836	T5834	conj	TTD,XP
R3974	T5837	T5838	punct	(,XPTTD
R3975	T5838	T5836	parataxis	XPTTD,TTD
R3976	T5839	T5838	punct	),XPTTD
R3977	T5840	T5841	punct	[,8
R3978	T5841	T5825	parataxis	8,associated
R3979	T5842	T5841	punct	],8
R398	T726	T724	pobj	outcomes,in
R3980	T5843	T5825	punct	.,associated
R3981	T5845	T5846	advcl	Similar,had
R3982	T5847	T5845	prep	to,Similar
R3983	T5848	T5849	det	the,mice
R3984	T5849	T5847	pobj	mice,to
R3985	T5850	T5851	nmod	XpdTTD,†XPCS
R3986	T5851	T5849	nmod	†XPCS,mice
R3987	T5852	T5851	punct	/,†XPCS
R3988	T5853	T5851	cc	and,†XPCS
R3989	T5854	T5855	compound	XpdTTD,†XP
R399	T727	T726	amod	phenotypic,outcomes
R3990	T5855	T5851	conj	†XP,†XPCS
R3991	T5856	T5855	punct	/,†XP
R3992	T5857	T5849	acl	described,mice
R3993	T5858	T5857	advmod	here,described
R3994	T5859	T5846	punct	", ",had
R3995	T5860	T5861	det	both,patients
R3996	T5861	T5846	nsubj	patients,had
R3997	T5862	T5861	prep	with,patients
R3998	T5863	T5862	pobj	XPTTD,with
R3999	T5864	T5861	acl	described,patients
R4	T89	T88	pobj	Trichothiodystrophy,in
R40	T127	T114	aux	has,documented
R400	T728	T726	prep	including,outcomes
R4000	T5865	T5866	advmod	so,far
R4001	T5866	T5864	advmod	far,described
R4002	T5867	T5868	amod	intermediate,values
R4003	T5868	T5846	dobj	values,had
R4004	T5869	T5870	compound	hair,cysteine
R4005	T5870	T5868	compound	cysteine,values
R4006	T5871	T5846	punct	.,had
R4007	T5873	T5874	advmod	Furthermore,carried
R4008	T5875	T5874	punct	", ",carried
R4009	T5876	T5877	compound	XPTTD,XP38BR
R401	T729	T730	amod	interallelic,complementation
R4010	T5877	T5874	nsubj	XP38BR,carried
R4011	T5878	T5877	compound	patient,XP38BR
R4012	T5879	T5880	det	a,mutation
R4013	T5880	T5874	dobj	mutation,carried
R4014	T5881	T5880	punct	“,mutation
R4015	T5882	T5880	amod	causative,mutation
R4016	T5883	T5880	punct	”,mutation
R4017	T5884	T5880	compound	TTD,mutation
R4018	T5885	T5874	prep	in,carried
R4019	T5886	T5887	nummod	one,allele
R402	T730	T728	pobj	complementation,including
R4020	T5887	T5885	pobj	allele,in
R4021	T5888	T5874	cc	and,carried
R4022	T5889	T5890	det	a,mutation
R4023	T5890	T5874	conj	mutation,carried
R4024	T5891	T5890	amod	novel,mutation
R4025	T5892	T5890	compound	point,mutation
R4026	T5893	T5890	acl	encoding,mutation
R4027	T5894	T5893	dobj	XPDL485P,encoding
R4028	T5895	T5890	prep	in,mutation
R4029	T5896	T5897	det	the,other
R403	T731	T692	punct	.,result
R4030	T5897	T5895	pobj	other,in
R4031	T5898	T5874	punct	.,carried
R4032	T5900	T5901	mark	Although,fails
R4033	T5901	T5907	advcl	fails,suggest
R4034	T5902	T5903	det	the,allele
R4035	T5903	T5901	nsubj	allele,fails
R4036	T5904	T5905	npadvmod	XPDL485P,encoding
R4037	T5905	T5903	amod	encoding,allele
R4038	T5906	T5905	punct	-,encoding
R4039	T5908	T5909	aux	to,complement
R404	T733	T734	mark	Although,create
R4040	T5909	T5901	xcomp	complement,fails
R4041	T5910	T5909	dobj	viability,complement
R4042	T5911	T5909	prep	in,complement
R4043	T5912	T5913	det	the,strain
R4044	T5913	T5911	pobj	strain,in
R4045	T5914	T5913	amod	haploid,strain
R4046	T5915	T5913	nmod	S.,strain
R4047	T5916	T5913	nmod	pombe,strain
R4048	T5917	T5913	compound	rad15,strain
R4049	T5918	T5913	compound	deletion,strain
R405	T734	T743	advcl	create,caused
R4050	T5919	T5901	cc	and,fails
R4051	T5920	T5901	conj	is,fails
R4052	T5921	T5920	advmod	thus,is
R4053	T5922	T5920	acomp	interpretable,is
R4054	T5923	T5922	prep	as,interpretable
R4055	T5924	T5925	det	a,allele
R4056	T5925	T5923	pobj	allele,as
R4057	T5926	T5925	amod	null,allele
R4058	T5927	T5928	punct	[,8
R4059	T5928	T5920	parataxis	8,is
R406	T735	T734	nsubj	amelioration,create
R4060	T5929	T5928	punct	],8
R4061	T5930	T5907	punct	", ",suggest
R4062	T5931	T5907	nsubj	we,suggest
R4063	T5932	T5907	advmod	nonetheless,suggest
R4064	T5933	T5934	mark	that,involves
R4065	T5934	T5907	ccomp	involves,suggest
R4066	T5935	T5936	det	the,phenotype
R4067	T5936	T5934	nsubj	phenotype,involves
R4068	T5937	T5936	amod	combined,phenotype
R4069	T5938	T5936	compound	XPTTD,phenotype
R407	T736	T735	prep	of,amelioration
R4070	T5939	T5936	prep	in,phenotype
R4071	T5940	T5941	det	this,patient
R4072	T5941	T5939	pobj	patient,in
R4073	T5942	T5943	amod	phenotypic,contributions
R4074	T5943	T5934	dobj	contributions,involves
R4075	T5944	T5943	prep	from,contributions
R4076	T5945	T5946	det	both,alleles
R4077	T5946	T5944	pobj	alleles,from
R4078	T5947	T5907	punct	.,suggest
R4079	T5949	T5950	advcl	Taken,suggest
R408	T737	T738	compound	disease,symptoms
R4080	T5951	T5949	advmod	together,Taken
R4081	T5952	T5950	punct	", ",suggest
R4082	T5953	T5954	det	these,data
R4083	T5954	T5950	nsubj	data,suggest
R4084	T5955	T5956	det	a,shift
R4085	T5956	T5950	dobj	shift,suggest
R4086	T5957	T5956	prep	to,shift
R4087	T5958	T5959	det	a,paradigm
R4088	T5959	T5957	pobj	paradigm,to
R4089	T5960	T5959	amod	biallelic,paradigm
R409	T738	T736	pobj	symptoms,of
R4090	T5961	T5959	prep	for,paradigm
R4091	T5962	T5963	nmod	compound,patients
R4092	T5963	T5961	pobj	patients,for
R4093	T5964	T5963	amod	heterozygous,patients
R4094	T5965	T5963	prep	in,patients
R4095	T5966	T5967	compound	XP,D
R4096	T5967	T5965	pobj	D,in
R4097	T5968	T5967	compound	complementation,D
R4098	T5969	T5967	compound	group,D
R4099	T5970	T5950	punct	.,suggest
R41	T128	T114	neg	not,documented
R410	T739	T735	prep	by,amelioration
R4100	T6042	T6041	prep	of,Potential
R4101	T6043	T6044	amod	Combined,Alleles
R4102	T6044	T6042	pobj	Alleles,of
R4103	T6045	T6044	amod	Recessive,Alleles
R4104	T6046	T6047	aux	to,Affect
R4105	T6047	T6041	acl	Affect,Potential
R4106	T6048	T6049	amod	Phenotypic,Diversity
R4107	T6049	T6047	dobj	Diversity,Affect
R4108	T6050	T6047	prep	in,Affect
R4109	T6051	T6050	pobj	Mammals,in
R411	T740	T741	amod	interallelic,complementation
R4110	T6053	T6054	prep	In,remains
R4111	T6055	T6053	pobj	humans,In
R4112	T6056	T6054	punct	", ",remains
R4113	T6057	T6058	det	the,relevance
R4114	T6058	T6054	nsubj	relevance,remains
R4115	T6059	T6058	amod	clinical,relevance
R4116	T6060	T6058	prep	of,relevance
R4117	T6061	T6062	amod	biallelic,effects
R4118	T6062	T6060	pobj	effects,of
R4119	T6063	T6064	amod	such,as
R412	T741	T739	pobj	complementation,by
R4120	T6064	T6062	prep	as,effects
R4121	T6065	T6066	amod	interallelic,complementation
R4122	T6066	T6064	pobj	complementation,as
R4123	T6067	T6054	acomp	unknown,remains
R4124	T6068	T6054	punct	.,remains
R4125	T6070	T6071	mark	Although,described
R4126	T6071	T6081	advcl	described,noted
R4127	T6072	T6073	amod	interallelic,complementation
R4128	T6073	T6071	nsubjpass	complementation,described
R4129	T6074	T6073	prep	between,complementation
R413	T742	T734	aux	would,create
R4130	T6075	T6076	nummod	two,alleles
R4131	T6076	T6074	pobj	alleles,between
R4132	T6077	T6076	amod	endogenous,alleles
R4133	T6078	T6076	amod	mutant,alleles
R4134	T6079	T6071	aux	has,described
R4135	T6080	T6071	auxpass	been,described
R4136	T6082	T6071	prep	in,described
R4137	T6083	T6082	pobj	cells,in
R4138	T6084	T6083	prep	from,cells
R4139	T6085	T6086	det	a,patient
R414	T744	T745	det	an,bias
R4140	T6086	T6084	pobj	patient,from
R4141	T6087	T6086	nmod	compound,patient
R4142	T6088	T6086	amod	heterozygous,patient
R4143	T6089	T6086	prep	with,patient
R4144	T6090	T6091	amod	methylmalonic,acidaemia
R4145	T6091	T6089	pobj	acidaemia,with
R4146	T6092	T6081	punct	", ",noted
R4147	T6093	T6094	det	no,effects
R4148	T6094	T6081	nsubjpass	effects,noted
R4149	T6095	T6094	amod	observable,effects
R415	T745	T734	dobj	bias,create
R4150	T6096	T6094	prep	on,effects
R4151	T6097	T6098	compound	disease,outcome
R4152	T6098	T6096	pobj	outcome,on
R4153	T6099	T6081	auxpass	were,noted
R4154	T6100	T6081	prep	in,noted
R4155	T6101	T6102	det	the,patient
R4156	T6102	T6100	pobj	patient,in
R4157	T6103	T6104	punct	[,28
R4158	T6104	T6081	parataxis	28,noted
R4159	T6105	T6104	punct	],28
R416	T746	T745	compound	ascertainment,bias
R4160	T6106	T6081	punct	.,noted
R4161	T6108	T6109	advmod	Thus,is
R4162	T6110	T6109	punct	", ",is
R4163	T6111	T6109	prep	to,is
R4164	T6112	T6113	det	the,best
R4165	T6113	T6111	pobj	best,to
R4166	T6114	T6113	prep	of,best
R4167	T6115	T6116	poss	our,knowledge
R4168	T6116	T6114	pobj	knowledge,of
R4169	T6117	T6109	punct	", ",is
R417	T747	T734	prep	in,create
R4170	T6118	T6119	det	the,amelioration
R4171	T6119	T6109	nsubj	amelioration,is
R4172	T6120	T6119	prep	of,amelioration
R4173	T6121	T6122	amod	progeroid,features
R4174	T6122	T6120	pobj	features,of
R4175	T6123	T6119	acl	observed,amelioration
R4176	T6124	T6123	advmod	here,observed
R4177	T6125	T6126	det	the,demonstration
R4178	T6126	T6109	attr	demonstration,is
R4179	T6127	T6126	amod	first,demonstration
R418	T748	T749	det	the,clinic
R4180	T6128	T6129	advmod	in,vivo
R4181	T6129	T6126	amod	vivo,demonstration
R4182	T6130	T6126	prep	in,demonstration
R4183	T6131	T6132	nmod	compound,animals
R4184	T6132	T6130	pobj	animals,in
R4185	T6133	T6132	amod	heterozygous,animals
R4186	T6134	T6132	prep	of,animals
R4187	T6135	T6136	amod	interallelic,complementation
R4188	T6136	T6134	pobj	complementation,of
R4189	T6137	T6126	amod	relevant,demonstration
R419	T749	T747	pobj	clinic,in
R4190	T6138	T6137	prep	to,relevant
R4191	T6139	T6140	det	a,disease
R4192	T6140	T6138	pobj	disease,to
R4193	T6141	T6140	amod	human,disease
R4194	T6142	T6109	punct	.,is
R4195	T6144	T6145	advcl	Keeping,is
R4196	T6146	T6144	prep	in,Keeping
R4197	T6147	T6146	pobj	mind,in
R4198	T6148	T6149	mark	that,result
R4199	T6149	T6144	ccomp	result,Keeping
R42	T129	T114	auxpass	been,documented
R420	T750	T743	punct	", ",caused
R4200	T6150	T6151	det	the,alleles
R4201	T6151	T6149	nsubj	alleles,result
R4202	T6152	T6153	punct	~,"1,200"
R4203	T6153	T6151	nummod	"1,200",alleles
R4204	T6154	T6151	acl	known,alleles
R4205	T6155	T6156	aux	to,exist
R4206	T6156	T6154	xcomp	exist,known
R4207	T6157	T6156	prep	for,exist
R4208	T6158	T6159	det	the,gene
R4209	T6159	T6157	pobj	gene,for
R421	T751	T752	det	the,lack
R4210	T6160	T6159	compound	CTRF,gene
R4211	T6161	T6159	acl	implicated,gene
R4212	T6162	T6161	prep	in,implicated
R4213	T6163	T6164	det	the,disorder
R4214	T6164	T6162	pobj	disorder,in
R4215	T6165	T6164	amod	common,disorder
R4216	T6166	T6164	amod	autosomal,disorder
R4217	T6167	T6164	amod	recessive,disorder
R4218	T6168	T6169	amod	cystic,fibrosis
R4219	T6169	T6164	appos	fibrosis,disorder
R422	T752	T743	nsubjpass	lack,caused
R4220	T6170	T6161	advmod	alone,implicated
R4221	T6171	T6172	punct	[,29
R4222	T6172	T6154	parataxis	29,known
R4223	T6173	T6172	punct	],29
R4224	T6174	T6149	aux	can,result
R4225	T6175	T6149	advmod	theoretically,result
R4226	T6176	T6149	prep	in,result
R4227	T6177	T6178	punct	~,"700,000"
R4228	T6178	T6179	nummod	"700,000",combinations
R4229	T6179	T6176	pobj	combinations,in
R423	T753	T752	prep	of,lack
R4230	T6180	T6179	amod	different,combinations
R4231	T6181	T6179	amod	allelic,combinations
R4232	T6182	T6145	punct	", ",is
R4233	T6183	T6184	det	the,number
R4234	T6184	T6145	nsubj	number,is
R4235	T6185	T6184	amod	potential,number
R4236	T6186	T6184	prep	of,number
R4237	T6187	T6188	amod	allelic,combinations
R4238	T6188	T6186	pobj	combinations,of
R4239	T6189	T6188	prep	of,combinations
R424	T754	T753	pobj	evidence,of
R4240	T6190	T6191	amod	different,mutations
R4241	T6191	T6189	pobj	mutations,of
R4242	T6192	T6191	amod	recessive,mutations
R4243	T6193	T6191	cc	and,mutations
R4244	T6194	T6195	amod	single,polymorphisms
R4245	T6195	T6191	conj	polymorphisms,mutations
R4246	T6196	T6195	compound	nucleotide,polymorphisms
R4247	T6197	T6198	npadvmod	genome,wide
R4248	T6198	T6184	amod	wide,number
R4249	T6199	T6198	punct	-,wide
R425	T755	T754	prep	concerning,evidence
R4250	T6200	T6145	advmod	currently,is
R4251	T6201	T6145	acomp	incalculable,is
R4252	T6202	T6145	punct	.,is
R4253	T6204	T6205	nsubj	We,suggest
R4254	T6206	T6207	amod	biallelic,effects
R4255	T6207	T6205	dobj	effects,suggest
R4256	T6208	T6205	prep	as,suggest
R4257	T6209	T6210	det	a,variable
R4258	T6210	T6208	pobj	variable,as
R4259	T6211	T6212	advmod	previously,underestimated
R426	T756	T757	amod	interallelic,complementation
R4260	T6212	T6213	amod	underestimated,important
R4261	T6213	T6210	amod	important,variable
R4262	T6214	T6213	advmod	yet,important
R4263	T6215	T6205	prep	in,suggest
R4264	T6216	T6215	pcomp	considering,in
R4265	T6217	T6218	compound	genotype,phenotype
R4266	T6218	T6220	compound	phenotype,relationships
R4267	T6219	T6218	punct	–,phenotype
R4268	T6220	T6216	dobj	relationships,considering
R4269	T6221	T6216	prep	from,considering
R427	T757	T755	pobj	complementation,concerning
R4270	T6222	T6223	amod	autosomal,disease
R4271	T6223	T6221	pobj	disease,from
R4272	T6224	T6223	amod	recessive,disease
R4273	T6225	T6221	prep	to,from
R4274	T6226	T6227	amod	normal,diversity
R4275	T6227	T6225	pobj	diversity,to
R4276	T6228	T6227	amod	phenotypic,diversity
R4277	T6229	T6216	prep	in,considering
R4278	T6230	T6229	pobj	mammals,in
R4279	T6231	T6205	punct	.,suggest
R428	T758	T757	cc	or,complementation
R4280	T6233	T6234	nsubj	Extension,implies
R4281	T6235	T6233	prep	of,Extension
R4282	T6236	T6237	det	the,concept
R4283	T6237	T6235	pobj	concept,of
R4284	T6238	T6237	amod	above,concept
R4285	T6239	T6240	mark	that,enter
R4286	T6240	T6234	ccomp	enter,implies
R4287	T6241	T6242	amod	recessive,mutations
R4288	T6242	T6240	nsubj	mutations,enter
R4289	T6243	T6240	aux	can,enter
R429	T759	T760	amod	other,effects
R4290	T6244	T6245	amod	evolutionary,selection
R4291	T6245	T6240	dobj	selection,enter
R4292	T6246	T6240	prep	in,enter
R4293	T6247	T6246	pobj	F1,in
R4294	T6248	T6240	prep	provided,enter
R4295	T6249	T6250	mark	that,carries
R4296	T6250	T6248	pcomp	carries,provided
R4297	T6251	T6252	det	the,allele
R4298	T6252	T6250	nsubj	allele,carries
R4299	T6253	T6252	amod	second,allele
R43	T130	T114	advmod	well,documented
R430	T760	T757	conj	effects,complementation
R4300	T6254	T6255	det	a,alteration
R4301	T6255	T6250	dobj	alteration,carries
R4302	T6256	T6255	amod	different,alteration
R4303	T6257	T6255	amod	recessive,alteration
R4304	T6258	T6234	punct	.,implies
R4305	T6260	T6261	advmod	Finally,highlight
R4306	T6262	T6261	punct	", ",highlight
R4307	T6263	T6264	poss	our,data
R4308	T6264	T6261	nsubj	data,highlight
R4309	T6265	T6266	det	the,potential
R431	T761	T760	amod	biallelic,effects
R4310	T6266	T6261	dobj	potential,highlight
R4311	T6267	T6266	prep	of,potential
R4312	T6268	T6269	advmod	clinically,relevant
R4313	T6269	T6270	amod	relevant,alleles
R4314	T6270	T6267	pobj	alleles,of
R4315	T6271	T6272	advmod	previously,designated
R4316	T6272	T6270	acl	designated,alleles
R4317	T6273	T6272	prep	as,designated
R4318	T6274	T6273	amod	null,as
R4319	T6275	T6270	punct	", ",alleles
R432	T762	T757	prep	in,complementation
R4320	T6276	T6270	prep	with,alleles
R4321	T6277	T6278	amod	little,expression
R4322	T6278	T6276	pobj	expression,with
R4323	T6279	T6277	cc	or,little
R4324	T6280	T6277	conj	no,little
R4325	T6281	T6278	amod	detectable,expression
R4326	T6282	T6278	cc	or,expression
R4327	T6283	T6278	conj	activity,expression
R4328	T6284	T6266	punct	", ",potential
R4329	T6285	T6286	aux	to,contribute
R433	T763	T764	amod	human,disease
R4330	T6286	T6266	acl	contribute,potential
R4331	T6287	T6286	advmod	nonetheless,contribute
R4332	T6288	T6286	prep	to,contribute
R4333	T6289	T6288	pobj	phenotype,to
R4334	T6290	T6261	punct	.,highlight
R4335	T6365	T6364	cc	and,Derivation
R4336	T6366	T6364	conj	analysis,Derivation
R4337	T6367	T6364	prep	of,Derivation
R4338	T6368	T6369	amod	mutant,mice
R4339	T6369	T6367	pobj	mice,of
R434	T764	T762	pobj	disease,in
R4340	T6370	T6364	punct	.,Derivation
R4341	T6372	T6373	nsubjpass	Generation,described
R4342	T6374	T6372	prep	of,Generation
R4343	T6375	T6376	nmod	XpdTTD,mice
R4344	T6376	T6374	pobj	mice,of
R4345	T6377	T6378	punct	(,XPDR722W
R4346	T6378	T6375	parataxis	XPDR722W,XpdTTD
R4347	T6379	T6378	punct	),XPDR722W
R4348	T6380	T6375	cc	and,XpdTTD
R4349	T6381	T6382	compound	XpdTTD,KO
R435	T765	T743	auxpass	is,caused
R4350	T6382	T6375	conj	KO,XpdTTD
R4351	T6383	T6382	punct	/,KO
R4352	T6384	T6373	aux	has,described
R4353	T6385	T6373	auxpass	been,described
R4354	T6386	T6373	advmod	previously,described
R4355	T6387	T6388	punct	[,22
R4356	T6388	T6373	parataxis	22,described
R4357	T6389	T6388	nummod	21,22
R4358	T6390	T6388	punct	",",22
R4359	T6391	T6388	punct	],22
R436	T766	T743	advmod	likely,caused
R4360	T6392	T6373	punct	.,described
R4361	T6394	T6395	det	A,description
R4362	T6395	T6397	nsubjpass	description,provided
R4363	T6396	T6395	amod	detailed,description
R4364	T6398	T6395	prep	of,description
R4365	T6399	T6400	det	the,generation
R4366	T6400	T6398	pobj	generation,of
R4367	T6401	T6400	prep	of,generation
R4368	T6402	T6403	amod	targeting,constructs
R4369	T6403	T6401	pobj	constructs,of
R437	T767	T743	agent	by,caused
R4370	T6404	T6403	prep	for,constructs
R4371	T6405	T6406	nmod	Xpd†XPCS,alleles
R4372	T6406	T6404	pobj	alleles,for
R4373	T6407	T6405	cc	and,Xpd†XPCS
R4374	T6408	T6405	conj	Xpd †XP,Xpd†XPCS
R4375	T6409	T6406	acl	carrying,alleles
R4376	T6410	T6409	dobj	mutations,carrying
R4377	T6411	T6410	acl	encoding,mutations
R4378	T6412	T6413	det	the,alterations
R4379	T6413	T6411	dobj	alterations,encoding
R438	T768	T769	det	the,difficulty
R4380	T6414	T6413	nmod	G602D,alterations
R4381	T6415	T6414	cc	and,G602D
R4382	T6416	T6414	conj	R683W,G602D
R4383	T6417	T6397	aux	will,provided
R4384	T6418	T6397	auxpass	be,provided
R4385	T6419	T6397	prep	upon,provided
R4386	T6420	T6419	pobj	request,upon
R4387	T6421	T6397	punct	.,provided
R4388	T6423	T6424	amod	Chimeric,fibroblasts
R4389	T6424	T6429	nsubjpass	fibroblasts,generated
R439	T769	T767	pobj	difficulty,by
R4390	T6425	T6424	nmod	mice,fibroblasts
R4391	T6426	T6425	cc	and,mice
R4392	T6427	T6428	npadvmod	mouse,embryonic
R4393	T6428	T6425	conj	embryonic,mice
R4394	T6430	T6429	auxpass	were,generated
R4395	T6431	T6429	prep	according,generated
R4396	T6432	T6431	prep	to,according
R4397	T6433	T6434	amod	standard,procedures
R4398	T6434	T6432	pobj	procedures,to
R4399	T6435	T6429	punct	.,generated
R44	T131	T114	punct	.,documented
R440	T770	T769	prep	in,difficulty
R4400	T6437	T6438	nmod	Haematoxylin,staining
R4401	T6438	T6441	nsubjpass	staining,performed
R4402	T6439	T6437	cc	and,Haematoxylin
R4403	T6440	T6437	conj	eosin,Haematoxylin
R4404	T6442	T6441	auxpass	was,performed
R4405	T6443	T6441	prep	according,performed
R4406	T6444	T6443	prep	to,according
R4407	T6445	T6446	amod	standard,procedures
R4408	T6446	T6444	pobj	procedures,to
R4409	T6447	T6441	punct	.,performed
R441	T771	T770	pcomp	distinguishing,in
R4410	T6449	T6450	compound	Amino,acid
R4411	T6450	T6451	compound	acid,analysis
R4412	T6451	T6452	nsubjpass	analysis,conducted
R4413	T6453	T6452	auxpass	was,conducted
R4414	T6454	T6455	mark	as,described
R4415	T6455	T6452	advcl	described,conducted
R4416	T6456	T6455	prep	in,described
R4417	T6457	T6456	punct	[,in
R4418	T6458	T6456	pobj	21,in
R4419	T6459	T6452	punct	],conducted
R442	T772	T773	amod	such,effects
R4420	T6460	T6452	punct	.,conducted
R4421	T6462	T6463	compound	Blood,values
R4422	T6463	T6464	nsubjpass	values,analysed
R4423	T6465	T6464	auxpass	were,analysed
R4424	T6466	T6464	advcl	using,analysed
R4425	T6467	T6468	nmod	Animal,Vet
R4426	T6468	T6466	dobj	Vet,using
R4427	T6469	T6468	nmod	Blood,Vet
R4428	T6470	T6468	amod	Counter,Vet
R4429	T6471	T6472	punct	(,Diagnostix
R443	T773	T771	dobj	effects,distinguishing
R4430	T6472	T6468	parataxis	Diagnostix,Vet
R4431	T6473	T6472	compound	ABX,Diagnostix
R4432	T6474	T6472	punct	", ",Diagnostix
R4433	T6475	T6472	npadvmod	Montpellier,Diagnostix
R4434	T6476	T6472	punct	", ",Diagnostix
R4435	T6477	T6472	npadvmod	France,Diagnostix
R4436	T6478	T6472	punct	),Diagnostix
R4437	T6479	T6464	punct	.,analysed
R4438	T6481	T6482	nsubjpass	Radiographs,taken
R4439	T6483	T6482	auxpass	were,taken
R444	T774	T771	prep	from,distinguishing
R4440	T6484	T6482	punct	", ",taken
R4441	T6485	T6482	cc	and,taken
R4442	T6486	T6487	amod	relative,density
R4443	T6487	T6490	nsubjpass	density,calculated
R4444	T6488	T6489	compound	bone,mineral
R4445	T6489	T6487	compound	mineral,density
R4446	T6490	T6482	conj	calculated,taken
R4447	T6491	T6490	auxpass	was,calculated
R4448	T6492	T6493	mark	as,described
R4449	T6493	T6490	advcl	described,calculated
R445	T775	T774	pobj	environment,from
R4450	T6494	T6493	prep	in,described
R4451	T6495	T6494	punct	[,in
R4452	T6496	T6494	pobj	15,in
R4453	T6497	T6490	punct	],calculated
R4454	T6498	T6490	punct	.,calculated
R4455	T6500	T6501	nsubj	Mice,were
R4456	T6502	T6500	acl	used,Mice
R4457	T6503	T6502	prep	in,used
R4458	T6504	T6505	det	this,study
R4459	T6505	T6503	pobj	study,in
R446	T776	T775	cc	and,environment
R4460	T6506	T6501	prep	in,were
R4461	T6507	T6508	det	a,background
R4462	T6508	T6506	pobj	background,in
R4463	T6509	T6510	nmod	129Ola,C57BL6
R4464	T6510	T6508	nmod	C57BL6,background
R4465	T6511	T6510	punct	/,C57BL6
R4466	T6512	T6508	amod	mixed,background
R4467	T6513	T6514	mark	unless,noted
R4468	T6514	T6501	advcl	noted,were
R4469	T6515	T6514	advmod	differently,noted
R447	T777	T778	amod	genetic,background
R4470	T6516	T6501	punct	.,were
R4471	T6518	T6519	det	All,experiments
R4472	T6519	T6520	nsubjpass	experiments,judged
R4473	T6521	T6519	acl	involving,experiments
R4474	T6522	T6521	dobj	mice,involving
R4475	T6523	T6520	auxpass	were,judged
R4476	T6524	T6520	cc	and,judged
R4477	T6525	T6520	conj	approved,judged
R4478	T6526	T6525	agent	by,approved
R4479	T6527	T6528	det	the,committee
R448	T778	T775	conj	background,environment
R4480	T6528	T6526	pobj	committee,by
R4481	T6529	T6528	amod	national,committee
R4482	T6530	T6528	prep	for,committee
R4483	T6531	T6532	amod	genetic,identification
R4484	T6532	T6530	pobj	identification,for
R4485	T6533	T6532	prep	of,identification
R4486	T6534	T6533	pobj	organisms,of
R4487	T6535	T6528	cc	and,committee
R4488	T6536	T6537	det	the,committee
R4489	T6537	T6528	conj	committee,committee
R449	T779	T743	punct	.,caused
R4490	T6538	T6537	nmod	animal,committee
R4491	T6539	T6537	amod	ethical,committee
R4492	T6540	T6520	punct	", ",judged
R4493	T6541	T6520	cc	and,judged
R4494	T6542	T6543	auxpass	were,conducted
R4495	T6543	T6520	conj	conducted,judged
R4496	T6544	T6543	prep	according,conducted
R4497	T6545	T6544	prep	to,according
R4498	T6546	T6547	amod	national,guidelines
R4499	T6547	T6545	pobj	guidelines,to
R45	T133	T134	nsubj	This,is
R450	T781	T782	nsubj	XPD,encodes
R4500	T6548	T6546	cc	and,national
R4501	T6549	T6546	conj	international,national
R4502	T6550	T6520	punct	.,judged
R4503	T6587	T6588	compound	UV,sensitivity
R4504	T6589	T6588	punct	", ",sensitivity
R4505	T6590	T6591	nmod	UV,UDS
R4506	T6591	T6593	nmod	UDS,activity
R4507	T6592	T6591	punct	-,UDS
R4508	T6593	T6588	appos	activity,sensitivity
R4509	T6594	T6591	punct	", ",UDS
R451	T783	T782	dobj	one,encodes
R4510	T6595	T6596	compound	UV,RRS
R4511	T6596	T6591	conj	RRS,UDS
R4512	T6597	T6596	punct	-,RRS
R4513	T6598	T6596	punct	", ",RRS
R4514	T6599	T6596	cc	and,RRS
R4515	T6600	T6596	conj	TFIIH,RRS
R4516	T6601	T6602	compound	incision,excision
R4517	T6602	T6593	compound	excision,activity
R4518	T6603	T6602	punct	/,excision
R4519	T6604	T6588	punct	.,sensitivity
R452	T784	T783	prep	of,one
R4520	T6606	T6607	nmod	UV,survival
R4521	T6607	T6608	nmod	survival,assays
R4522	T6608	T6618	nsubjpass	assays,performed
R4523	T6609	T6607	punct	", ",survival
R4524	T6610	T6611	compound	UV,UDS
R4525	T6611	T6607	conj	UDS,survival
R4526	T6612	T6611	punct	-,UDS
R4527	T6613	T6611	punct	", ",UDS
R4528	T6614	T6611	cc	and,UDS
R4529	T6615	T6616	compound	UV,RRS
R453	T785	T786	det	the,components
R4530	T6616	T6611	conj	RRS,UDS
R4531	T6617	T6616	punct	-,RRS
R4532	T6619	T6618	auxpass	were,performed
R4533	T6620	T6621	mark	as,described
R4534	T6621	T6618	advcl	described,performed
R4535	T6622	T6621	advmod	previously,described
R4536	T6623	T6624	punct	[,30
R4537	T6624	T6618	parataxis	30,performed
R4538	T6625	T6624	nummod	21,30
R4539	T6626	T6624	punct	",",30
R454	T786	T784	pobj	components,of
R4540	T6627	T6624	punct	],30
R4541	T6628	T6618	punct	.,performed
R4542	T6630	T6631	prep	For,presented
R4543	T6632	T6633	compound	UV,RRS
R4544	T6633	T6630	pobj	RRS,For
R4545	T6634	T6633	punct	-,RRS
R4546	T6635	T6631	punct	", ",presented
R4547	T6636	T6637	amod	average,values
R4548	T6637	T6631	nsubjpass	values,presented
R4549	T6638	T6637	prep	from,values
R455	T787	T786	nummod	two,components
R4550	T6639	T6640	det	the,experiment
R4551	T6640	T6638	pobj	experiment,from
R4552	T6641	T6640	amod	representative,experiment
R4553	T6642	T6640	acl	containing,experiment
R4554	T6643	T6644	nummod	two,wt
R4555	T6644	T6645	nmod	wt,line
R4556	T6645	T6642	dobj	line,containing
R4557	T6646	T6644	punct	", ",wt
R4558	T6647	T6648	nummod	three,TTD
R4559	T6648	T6644	conj	TTD,wt
R456	T788	T786	compound	helicase,components
R4560	T6649	T6648	compound	XpdTTD,TTD
R4561	T6650	T6648	punct	/,TTD
R4562	T6651	T6648	punct	", ",TTD
R4563	T6652	T6653	nummod	two,XPCS
R4564	T6653	T6648	conj	XPCS,TTD
R4565	T6654	T6653	compound	XpdTTD,XPCS
R4566	T6655	T6653	punct	/,XPCS
R4567	T6656	T6653	punct	", ",XPCS
R4568	T6657	T6653	cc	and,XPCS
R4569	T6658	T6659	nummod	one,XP
R457	T789	T786	prep	of,components
R4570	T6659	T6653	conj	XP,XPCS
R4571	T6660	T6659	compound	XpdTTD,XP
R4572	T6661	T6659	punct	/,XP
R4573	T6662	T6645	compound	cell,line
R4574	T6663	T6631	auxpass	are,presented
R4575	T6664	T6631	punct	.,presented
R4576	T6666	T6667	det	The,value
R4577	T6667	T6674	nsubj	value,differs
R4578	T6668	T6669	punct	~,48
R4579	T6669	T6670	nummod	48,%
R458	T790	T791	amod	basal,IIH
R4580	T6670	T6667	compound	%,value
R4581	T6671	T6672	compound	UV,UDS
R4582	T6672	T6667	compound	UDS,value
R4583	T6673	T6672	punct	-,UDS
R4584	T6675	T6667	acl	presented,value
R4585	T6676	T6675	prep	in,presented
R4586	T6677	T6678	det	this,study
R4587	T6678	T6676	pobj	study,in
R4588	T6679	T6667	prep	for,value
R4589	T6680	T6681	compound	XpdTTD,TTD
R459	T791	T789	pobj	IIH,of
R4590	T6681	T6683	compound	TTD,cells
R4591	T6682	T6681	punct	/,TTD
R4592	T6683	T6679	pobj	cells,for
R4593	T6684	T6674	prep	from,differs
R4594	T6685	T6686	poss	our,data
R4595	T6686	T6684	pobj	data,from
R4596	T6687	T6688	advmod	previously,published
R4597	T6688	T6686	amod	published,data
R4598	T6689	T6686	prep	of,data
R4599	T6690	T6691	nummod	25,%
R46	T135	T136	advmod	most,likely
R460	T792	T791	nmod	transcription,IIH
R4600	T6691	T6692	compound	%,UDS
R4601	T6692	T6689	pobj	UDS,of
R4602	T6693	T6692	compound	UV,UDS
R4603	T6694	T6692	punct	-,UDS
R4604	T6695	T6696	punct	[,21
R4605	T6696	T6674	parataxis	21,differs
R4606	T6697	T6696	punct	],21
R4607	T6698	T6674	punct	", ",differs
R4608	T6699	T6700	advmod	possibly,because
R4609	T6700	T6674	prep	because,differs
R461	T793	T792	punct	/,transcription
R4610	T6701	T6700	prep	of,because
R4611	T6702	T6703	det	the,variability
R4612	T6703	T6701	pobj	variability,of
R4613	T6704	T6703	amod	high,variability
R4614	T6705	T6703	amod	intrinsic,variability
R4615	T6706	T6705	prep	to,intrinsic
R4616	T6707	T6708	det	the,assay
R4617	T6708	T6706	pobj	assay,to
R4618	T6709	T6708	cc	or,assay
R4619	T6710	T6711	amod	routine,variations
R462	T794	T795	compound	DNA,repair
R4620	T6711	T6708	conj	variations,assay
R4621	T6712	T6708	prep	in,assay
R4622	T6713	T6714	det	the,conditions
R4623	T6714	T6712	pobj	conditions,in
R4624	T6715	T6716	compound	cell,culture
R4625	T6716	T6714	compound	culture,conditions
R4626	T6717	T6674	punct	.,differs
R4627	T6719	T6720	prep	For,prepared
R4628	T6721	T6722	det	the,assay
R4629	T6722	T6719	pobj	assay,For
R463	T795	T792	appos	repair,transcription
R4630	T6723	T6724	compound	incision,excision
R4631	T6724	T6722	compound	excision,assay
R4632	T6725	T6724	punct	/,excision
R4633	T6726	T6722	compound	activity,assay
R4634	T6727	T6720	punct	", ",prepared
R4635	T6728	T6729	amod	recombinant,TFIIH
R4636	T6729	T6720	nsubjpass	TFIIH,prepared
R4637	T6730	T6720	auxpass	was,prepared
R4638	T6731	T6720	cc	and,prepared
R4639	T6732	T6720	conj	assayed,prepared
R464	T796	T791	compound	factor,IIH
R4640	T6733	T6734	mark	as,described
R4641	T6734	T6732	advcl	described,assayed
R4642	T6735	T6734	advmod	previously,described
R4643	T6736	T6737	punct	[,27
R4644	T6737	T6732	parataxis	27,assayed
R4645	T6738	T6737	punct	],27
R4646	T6739	T6720	punct	.,prepared
R4649	T6770	T6771	amod	Comparative,immunofluorescence
R465	T797	T791	punct	(,IIH
R4650	T6772	T6771	punct	.,immunofluorescence
R4651	T6774	T6775	compound	Latex,labelling
R4652	T6775	T6777	nsubjpass	labelling,performed
R4653	T6776	T6775	compound	bead,labelling
R4654	T6778	T6775	cc	and,labelling
R4655	T6779	T6780	amod	comparative,analysis
R4656	T6780	T6775	conj	analysis,labelling
R4657	T6781	T6780	compound	immunofluorescence,analysis
R4658	T6782	T6780	prep	of,analysis
R4659	T6783	T6784	det	the,subunit
R466	T798	T791	appos	TFIIH,IIH
R4660	T6784	T6782	pobj	subunit,of
R4661	T6785	T6784	compound	p62,subunit
R4662	T6786	T6784	prep	of,subunit
R4663	T6787	T6788	det	the,TFIIH
R4664	T6788	T6786	pobj	TFIIH,of
R4665	T6789	T6777	auxpass	was,performed
R4666	T6790	T6791	mark	as,described
R4667	T6791	T6777	advcl	described,performed
R4668	T6792	T6791	advmod	previously,described
R4669	T6793	T6794	punct	[,17
R467	T799	T783	punct	),one
R4670	T6794	T6791	parataxis	17,described
R4671	T6795	T6794	nummod	16,17
R4672	T6796	T6794	punct	",",17
R4673	T6797	T6794	punct	],17
R4674	T6798	T6777	advcl	using,performed
R4675	T6799	T6800	amod	primary,fibroblasts
R4676	T6800	T6798	dobj	fibroblasts,using
R4677	T6801	T6800	nmod	mouse,fibroblasts
R4678	T6802	T6800	amod	embryonic,fibroblasts
R4679	T6803	T6798	prep	at,using
R468	T800	T783	punct	", ",one
R4680	T6804	T6805	nmod	passages,2
R4681	T6805	T6803	pobj	2,at
R4682	T6806	T6807	punct	–,5
R4683	T6807	T6805	prep	5,2
R4684	T6808	T6777	punct	.,performed
R4685	T6810	T6811	nummod	Two,lines
R4686	T6811	T6815	nsubjpass	lines,used
R4687	T6812	T6810	cc	or,Two
R4688	T6813	T6810	conj	more,Two
R4689	T6814	T6811	compound	cell,lines
R469	T801	T802	det	a,complex
R4690	T6816	T6811	prep	per,lines
R4691	T6817	T6816	pobj	genotype,per
R4692	T6818	T6819	punct	(,except
R4693	T6819	T6811	parataxis	except,lines
R4694	T6820	T6819	prep	for,except
R4695	T6821	T6822	det	the,cells
R4696	T6822	T6820	pobj	cells,for
R4697	T6823	T6824	compound	XpdTTD,†XP
R4698	T6824	T6822	compound	†XP,cells
R4699	T6825	T6824	punct	/,†XP
R47	T136	T137	advmod	likely,because
R470	T802	T783	appos	complex,one
R4700	T6826	T6822	punct	", ",cells
R4701	T6827	T6828	prep	in,used
R4702	T6828	T6822	relcl	used,cells
R4703	T6829	T6827	pobj	which,in
R4704	T6830	T6831	advmod	only,line
R4705	T6831	T6828	nsubjpass	line,used
R4706	T6832	T6831	nummod	one,line
R4707	T6833	T6831	compound	cell,line
R4708	T6834	T6828	auxpass	was,used
R4709	T6835	T6828	prep	in,used
R471	T803	T804	nummod	ten,subunit
R4710	T6836	T6837	amod	repeated,experiments
R4711	T6837	T6835	pobj	experiments,in
R4712	T6838	T6819	punct	),except
R4713	T6839	T6815	auxpass	were,used
R4714	T6840	T6815	punct	", ",used
R4715	T6841	T6815	cc	and,used
R4716	T6842	T6843	nsubjpass	experiments,repeated
R4717	T6843	T6815	conj	repeated,used
R4718	T6844	T6843	auxpass	were,repeated
R4719	T6845	T6846	compound	2,6
R472	T804	T802	nmod	subunit,complex
R4720	T6846	T6848	nummod	6,times
R4721	T6847	T6846	punct	–,6
R4722	T6848	T6843	dobj	times,repeated
R4723	T6849	T6848	prep	per,times
R4724	T6850	T6849	pobj	genotype,per
R4725	T6851	T6843	punct	.,repeated
R4726	T7096	T7095	prep	of,Targeting
R4727	T7097	T7098	det	the,Gene
R4728	T7098	T7096	pobj	Gene,of
R4729	T7099	T7098	compound	Mouse,Gene
R473	T805	T804	punct	-,subunit
R4730	T7100	T7098	compound	Xpd,Gene
R4731	T7102	T7103	punct	(,A
R4732	T7103	T7104	meta	A,representation
R4733	T7105	T7103	punct	),A
R4734	T7106	T7104	amod	Schematic,representation
R4735	T7107	T7104	prep	of,representation
R4736	T7108	T7109	det	the,structure
R4737	T7109	T7107	pobj	structure,of
R4738	T7110	T7109	amod	genomic,structure
R4739	T7111	T7104	cc	and,representation
R474	T806	T802	punct	", ",complex
R4740	T7112	T7113	amod	partial,map
R4741	T7113	T7104	conj	map,representation
R4742	T7114	T7113	compound	restriction,map
R4743	T7115	T7113	prep	of,map
R4744	T7116	T7117	det	the,loci
R4745	T7117	T7115	pobj	loci,of
R4746	T7118	T7117	nmod	wt,loci
R4747	T7119	T7118	cc	and,wt
R4748	T7120	T7118	conj	targeted,wt
R4749	T7121	T7117	compound	mouse,loci
R475	T807	T802	amod	multifunctional,complex
R4750	T7122	T7117	compound	Xpd,loci
R4751	T7123	T7113	punct	.,map
R4752	T7125	T7126	prep	For,represented
R4753	T7127	T7128	det	the,allele
R4754	T7128	T7125	pobj	allele,For
R4755	T7129	T7128	compound	wt,allele
R4756	T7130	T7128	compound	Xpd,allele
R4757	T7131	T7126	punct	", ",represented
R4758	T7132	T7133	amod	shaded,boxes
R4759	T7133	T7134	nsubj	boxes,represent
R476	T808	T809	dep	that,is
R4760	T7134	T7126	ccomp	represent,represented
R4761	T7135	T7136	amod	coding,regions
R4762	T7136	T7134	dobj	regions,represent
R4763	T7137	T7136	prep	of,regions
R4764	T7138	T7139	nmod	exons,12
R4765	T7139	T7137	pobj	12,of
R4766	T7140	T7139	cc	and,12
R4767	T7141	T7139	conj	19,12
R4768	T7142	T7143	punct	–,23
R4769	T7143	T7141	prep	23,19
R477	T809	T802	relcl	is,complex
R4770	T7144	T7126	punct	;,represented
R4771	T7145	T7146	det	the,UTR
R4772	T7146	T7126	nsubjpass	UTR,represented
R4773	T7147	T7146	nummod	3,UTR
R4774	T7148	T7147	punct	′,3
R4775	T7149	T7126	auxpass	is,represented
R4776	T7150	T7126	agent	by,represented
R4777	T7151	T7152	det	an,box
R4778	T7152	T7150	pobj	box,by
R4779	T7153	T7152	amod	open,box
R478	T810	T809	acomp	essential,is
R4780	T7154	T7126	punct	.,represented
R4781	T7156	T7157	nsubj	TGA,indicates
R4782	T7157	T7158	ccomp	indicates,indicates
R4783	T7159	T7160	det	the,codon
R4784	T7160	T7157	dobj	codon,indicates
R4785	T7161	T7160	amod	translational,codon
R4786	T7162	T7160	compound	stop,codon
R4787	T7163	T7158	punct	;,indicates
R4788	T7164	T7158	nsubj	PolyA,indicates
R4789	T7165	T7166	det	the,signal
R479	T811	T810	prep	for,essential
R4790	T7166	T7158	dobj	signal,indicates
R4791	T7167	T7166	compound	polyadenylation,signal
R4792	T7168	T7158	punct	.,indicates
R4793	T7170	T7171	prep	For,indicated
R4794	T7172	T7173	det	the,allele
R4795	T7173	T7170	pobj	allele,For
R4796	T7174	T7173	nmod	XpdTTD,allele
R4797	T7175	T7173	amod	targeted,allele
R4798	T7176	T7171	punct	", ",indicated
R4799	T7177	T7178	det	the,fragment
R48	T137	T134	prep	because,is
R480	T812	T813	amod	multiple,processes
R4800	T7178	T7171	nsubjpass	fragment,indicated
R4801	T7179	T7180	nummod	194,pair
R4802	T7180	T7178	nmod	pair,fragment
R4803	T7181	T7180	punct	–,pair
R4804	T7182	T7180	nmod	base,pair
R4805	T7183	T7180	punct	(,pair
R4806	T7184	T7180	appos	bp,pair
R4807	T7185	T7178	punct	),fragment
R4808	T7186	T7178	amod	human,fragment
R4809	T7187	T7178	compound	XPD,fragment
R481	T813	T811	pobj	processes,for
R4810	T7188	T7178	compound	cDNA,fragment
R4811	T7189	T7178	acl	fused,fragment
R4812	T7190	T7189	prep	to,fused
R4813	T7191	T7190	pobj	exon,to
R4814	T7192	T7191	nummod	22,exon
R4815	T7193	T7171	auxpass	is,indicated
R4816	T7194	T7171	prep	as,indicated
R4817	T7195	T7196	det	a,box
R4818	T7196	T7194	pobj	box,as
R4819	T7197	T7196	amod	striped,box
R482	T814	T813	punct	", ",processes
R4820	T7198	T7171	prep	including,indicated
R4821	T7199	T7200	det	the,mutation
R4822	T7200	T7198	pobj	mutation,including
R4823	T7201	T7200	nmod	TTD,mutation
R4824	T7202	T7203	punct	(,R722W
R4825	T7203	T7201	parataxis	R722W,TTD
R4826	T7204	T7203	punct	),R722W
R4827	T7205	T7200	acl	indicated,mutation
R4828	T7206	T7205	agent	by,indicated
R4829	T7207	T7208	det	a,arrow
R483	T815	T813	prep	including,processes
R4830	T7208	T7206	pobj	arrow,by
R4831	T7209	T7208	amod	vertical,arrow
R4832	T7210	T7171	punct	.,indicated
R4833	T7212	T7213	nmod	Chicken,2
R4834	T7213	T7218	nsubjpass	2,indicated
R4835	T7214	T7215	nmod	β,globin
R4836	T7215	T7213	nmod	globin,2
R4837	T7216	T7215	punct	-,globin
R4838	T7217	T7213	nmod	exons,2
R4839	T7219	T7213	cc	and,2
R484	T816	T817	amod	basal,initiation
R4840	T7220	T7213	conj	3,2
R4841	T7221	T7213	prep	including,2
R4842	T7222	T7223	det	the,UTR
R4843	T7223	T7221	pobj	UTR,including
R4844	T7224	T7223	nummod	3,UTR
R4845	T7225	T7224	punct	′,3
R4846	T7226	T7218	auxpass	are,indicated
R4847	T7227	T7218	prep	as,indicated
R4848	T7228	T7229	amod	black,boxes
R4849	T7229	T7227	pobj	boxes,as
R485	T817	T815	pobj	initiation,including
R4850	T7230	T7229	prep	with,boxes
R4851	T7231	T7232	amod	corresponding,numerals
R4852	T7232	T7230	pobj	numerals,with
R4853	T7233	T7232	compound	Roman,numerals
R4854	T7234	T7232	acl	followed,numerals
R4855	T7235	T7234	agent	by,followed
R4856	T7236	T7237	det	the,signal
R4857	T7237	T7235	pobj	signal,by
R4858	T7238	T7239	compound	β,globin
R4859	T7239	T7237	compound	globin,signal
R486	T818	T817	compound	transcription,initiation
R4860	T7240	T7239	punct	-,globin
R4861	T7241	T7237	compound	polyadenylation,signal
R4862	T7242	T7243	punct	(,PolyA*
R4863	T7243	T7237	parataxis	PolyA*,signal
R4864	T7244	T7243	punct	),PolyA*
R4865	T7245	T7218	punct	.,indicated
R4866	T7247	T7248	prep	For,indicate
R4867	T7249	T7250	det	the,alleles
R4868	T7250	T7247	pobj	alleles,For
R4869	T7251	T7250	nmod	Xpd†XP,alleles
R487	T819	T817	cc	and,initiation
R4870	T7252	T7251	cc	and,Xpd†XP
R4871	T7253	T7251	conj	Xpd†XPCS,Xpd†XP
R4872	T7254	T7250	amod	targeted,alleles
R4873	T7255	T7248	punct	", ",indicate
R4874	T7256	T7257	amod	vertical,arrows
R4875	T7257	T7248	nsubj	arrows,indicate
R4876	T7258	T7259	nmod	XPCS,mutations
R4877	T7259	T7248	dobj	mutations,indicate
R4878	T7260	T7261	punct	(,encoding
R4879	T7261	T7258	parataxis	encoding,XPCS
R488	T820	T821	compound	DNA,repair
R4880	T7262	T7261	npadvmod	G602D,encoding
R4881	T7263	T7261	punct	-,encoding
R4882	T7264	T7261	punct	),encoding
R4883	T7265	T7258	cc	and,XPCS
R4884	T7266	T7258	conj	XP,XPCS
R4885	T7267	T7268	punct	(,encoding
R4886	T7268	T7266	parataxis	encoding,XP
R4887	T7269	T7268	npadvmod	R683W,encoding
R4888	T7270	T7268	punct	-,encoding
R4889	T7271	T7268	punct	),encoding
R489	T821	T817	conj	repair,initiation
R4890	T7272	T7259	prep	in,mutations
R4891	T7273	T7274	nmod	exons,19
R4892	T7274	T7272	pobj	19,in
R4893	T7275	T7274	cc	and,19
R4894	T7276	T7274	conj	22,19
R4895	T7277	T7248	punct	", ",indicate
R4896	T7278	T7248	advmod	respectively,indicate
R4897	T7279	T7248	punct	.,indicate
R4898	T7281	T7282	det	The,probe
R4899	T7282	T7286	nsubjpass	probe,marked
R49	T138	T137	pcomp	of,because
R490	T822	T821	compound	damage,repair
R4900	T7283	T7282	amod	unique,probe
R4901	T7284	T7282	nummod	3,probe
R4902	T7285	T7284	punct	′,3
R4903	T7287	T7282	acl	located,probe
R4904	T7288	T7287	prep	outside,located
R4905	T7289	T7290	det	the,construct
R4906	T7290	T7288	pobj	construct,outside
R4907	T7291	T7290	amod	targeting,construct
R4908	T7292	T7286	auxpass	is,marked
R4909	T7293	T7286	agent	by,marked
R491	T823	T821	prep	via,repair
R4910	T7294	T7295	det	a,line
R4911	T7295	T7293	pobj	line,by
R4912	T7296	T7295	amod	thick,line
R4913	T7297	T7295	amod	black,line
R4914	T7298	T7286	punct	.,marked
R4915	T7300	T7301	compound	Restriction,sites
R4916	T7302	T7301	punct	: ,sites
R4917	T7303	T7301	appos	B,sites
R4918	T7304	T7303	punct	", ",B
R4919	T7305	T7303	appos	BamHI,B
R492	T824	T825	det	the,pathway
R4920	T7306	T7303	punct	;,B
R4921	T7307	T7303	appos	C,B
R4922	T7308	T7307	punct	", ",C
R4923	T7309	T7307	appos	ClaI,C
R4924	T7310	T7303	punct	;,B
R4925	T7311	T7303	appos	E,B
R4926	T7312	T7311	punct	", ",E
R4927	T7313	T7311	appos	EcoRI,E
R4928	T7314	T7303	punct	;,B
R4929	T7315	T7303	appos	H,B
R493	T825	T823	pobj	pathway,via
R4930	T7316	T7315	punct	", ",H
R4931	T7317	T7315	appos	HindIII,H
R4932	T7318	T7303	punct	;,B
R4933	T7319	T7303	appos	Hp,B
R4934	T7320	T7319	punct	", ",Hp
R4935	T7321	T7319	appos	HpaI,Hp
R4936	T7322	T7303	punct	;,B
R4937	T7323	T7303	appos	Sf,B
R4938	T7324	T7323	punct	", ",Sf
R4939	T7325	T7323	appos	SfiI,Sf
R494	T826	T827	nmod	nucleotide,repair
R4940	T7326	T7301	punct	.,sites
R4941	T7328	T7329	punct	(,B
R4942	T7329	T7330	meta	B,analysis
R4943	T7331	T7329	punct	),B
R4944	T7332	T7333	compound	Southern,blot
R4945	T7333	T7330	compound	blot,analysis
R4946	T7334	T7330	prep	of,analysis
R4947	T7335	T7336	npadvmod	EcoRI,digested
R4948	T7336	T7338	amod	digested,DNA
R4949	T7337	T7336	punct	-,digested
R495	T827	T825	nmod	repair,pathway
R4950	T7338	T7334	pobj	DNA,of
R4951	T7339	T7338	amod	genomic,DNA
R4952	T7340	T7338	prep	from,DNA
R4953	T7341	T7342	nmod	wt,clones
R4954	T7342	T7340	pobj	clones,from
R4955	T7343	T7341	punct	", ",wt
R4956	T7344	T7345	compound	Xpd†XPCS,wt
R4957	T7345	T7341	conj	wt,wt
R4958	T7346	T7345	punct	/,wt
R4959	T7347	T7345	punct	", ",wt
R496	T828	T827	nmod	excision,repair
R4960	T7348	T7345	cc	and,wt
R4961	T7349	T7350	compound	Xpd†XP,wt
R4962	T7350	T7345	conj	wt,wt
R4963	T7351	T7350	punct	/,wt
R4964	T7352	T7342	amod	recombinant,clones
R4965	T7353	T7354	amod	embryonic,cell
R4966	T7354	T7342	compound	cell,clones
R4967	T7355	T7354	compound	stem,cell
R4968	T7356	T7342	acl	hybridised,clones
R4969	T7357	T7356	prep	with,hybridised
R497	T829	T827	punct	(,repair
R4970	T7358	T7359	det	the,probe
R4971	T7359	T7357	pobj	probe,with
R4972	T7360	T7359	nummod	3,probe
R4973	T7361	T7360	punct	′,3
R4974	T7362	T7359	acl	depicted,probe
R4975	T7363	T7362	prep	in,depicted
R4976	T7364	T7363	punct	(,in
R4977	T7365	T7363	pobj	A,in
R4978	T7366	T7330	punct	),analysis
R4979	T7367	T7330	punct	.,analysis
R498	T830	T827	appos	NER,repair
R4980	T7369	T7370	det	The,allele
R4981	T7370	T7372	nsubj	allele,yields
R4982	T7371	T7370	compound	wt,allele
R4983	T7373	T7374	det	a,fragment
R4984	T7374	T7372	dobj	fragment,yields
R4985	T7375	T7376	nummod	6.5,kilobase
R4986	T7376	T7374	nmod	kilobase,fragment
R4987	T7377	T7376	punct	-,kilobase
R4988	T7378	T7376	punct	(,kilobase
R4989	T7379	T7376	appos	kb,kilobase
R499	T831	T825	punct	),pathway
R4990	T7380	T7374	punct	),fragment
R4991	T7381	T7372	punct	", ",yields
R4992	T7382	T7383	mark	whereas,yield
R4993	T7383	T7372	advcl	yield,yields
R4994	T7384	T7385	preconj	both,alleles
R4995	T7385	T7383	nsubj	alleles,yield
R4996	T7386	T7385	amod	targeted,alleles
R4997	T7387	T7385	nmod	Xpd†XP,alleles
R4998	T7388	T7387	cc	and,Xpd†XP
R4999	T7389	T7387	conj	Xpd†XPCS,Xpd†XP
R5	T90	T84	prep	by,Rescue
R50	T139	T140	det	the,difficulty
R500	T832	T833	punct	[,7
R5000	T7390	T7391	det	a,fragment
R5001	T7391	T7383	dobj	fragment,yield
R5002	T7392	T7393	nummod	5.1,kb
R5003	T7393	T7391	compound	kb,fragment
R5004	T7394	T7393	punct	-,kb
R5005	T7395	T7372	punct	.,yields
R5006	T7397	T7398	punct	(,C
R5007	T7398	T7399	meta	C,Genotyping
R5008	T7400	T7398	punct	),C
R5009	T7401	T7399	prep	of,Genotyping
R501	T833	T783	parataxis	7,one
R5010	T7402	T7403	nmod	wt,alleles
R5011	T7403	T7401	pobj	alleles,of
R5012	T7404	T7402	cc	and,wt
R5013	T7405	T7402	conj	targeted,wt
R5014	T7406	T7399	prep	by,Genotyping
R5015	T7407	T7406	pobj	PCR,by
R5016	T7408	T7399	acl	using,Genotyping
R5017	T7409	T7408	dobj	primers,using
R5018	T7410	T7409	appos	F2,primers
R5019	T7411	T7410	punct	", ",F2
R502	T834	T833	nummod	6,7
R5020	T7412	T7410	conj	R1,F2
R5021	T7413	T7412	punct	", ",R1
R5022	T7414	T7412	cc	and,R1
R5023	T7415	T7412	conj	mR,R1
R5024	T7416	T7417	mark	as,indicated
R5025	T7417	T7408	advcl	indicated,using
R5026	T7418	T7408	prep	in,using
R5027	T7419	T7420	punct	(,A
R5028	T7420	T7421	meta	A,fragments
R5029	T7421	T7418	pobj	fragments,in
R503	T835	T833	punct	",",7
R5030	T7422	T7420	punct	),A
R5031	T7423	T7421	nmod	yields,fragments
R5032	T7424	T7421	prep	of,fragments
R5033	T7425	T7426	nummod	399,bp
R5034	T7426	T7424	pobj	bp,of
R5035	T7427	T7426	cc	and,bp
R5036	T7428	T7429	nummod	468,bp
R5037	T7429	T7426	conj	bp,bp
R5038	T7430	T7408	punct	", ",using
R5039	T7431	T7408	advmod	respectively,using
R504	T836	T833	punct	],7
R5040	T7432	T7399	punct	.,Genotyping
R5041	T7434	T7435	punct	(,D
R5042	T7435	T7436	meta	D,results
R5043	T7437	T7435	punct	),D
R5044	T7438	T7439	compound	RT,PCR
R5045	T7439	T7441	compound	PCR,detection
R5046	T7440	T7439	punct	-,PCR
R5047	T7441	T7436	nsubj	detection,results
R5048	T7442	T7441	prep	of,detection
R5049	T7443	T7444	compound	mRNA,expression
R505	T837	T782	punct	.,encodes
R5050	T7444	T7442	pobj	expression,of
R5051	T7445	T7444	acl	originating,expression
R5052	T7446	T7445	prep	from,originating
R5053	T7447	T7448	det	the,alleles
R5054	T7448	T7446	pobj	alleles,from
R5055	T7449	T7448	amod	targeted,alleles
R5056	T7450	T7448	nmod	†XP,alleles
R5057	T7451	T7450	cc	and,†XP
R5058	T7452	T7450	conj	†XPCS,†XP
R5059	T7453	T7441	prep	in,detection
R506	T839	T840	nsubjpass	Alterations,associated
R5060	T7454	T7455	amod	embryonic,cell
R5061	T7455	T7457	compound	cell,clones
R5062	T7456	T7455	compound	stem,cell
R5063	T7457	T7453	pobj	clones,in
R5064	T7458	T7441	acl	using,detection
R5065	T7459	T7458	dobj	primers,using
R5066	T7460	T7459	appos	F1,primers
R5067	T7461	T7462	punct	(,hybridising
R5068	T7462	T7460	parataxis	hybridising,F1
R5069	T7463	T7462	prep	outside,hybridising
R507	T841	T839	prep	in,Alterations
R5070	T7464	T7465	det	the,construct
R5071	T7465	T7463	pobj	construct,outside
R5072	T7466	T7465	amod	targeting,construct
R5073	T7467	T7462	punct	),hybridising
R5074	T7468	T7460	cc	and,F1
R5075	T7469	T7460	conj	mR,F1
R5076	T7470	T7471	mark	as,indicated
R5077	T7471	T7458	advcl	indicated,using
R5078	T7472	T7471	prep	in,indicated
R5079	T7473	T7472	punct	(,in
R508	T842	T841	pobj	XPD,in
R5080	T7474	T7472	pobj	A,in
R5081	T7475	T7436	punct	),results
R5082	T7476	T7436	prep	in,results
R5083	T7477	T7478	det	a,fragment
R5084	T7478	T7476	pobj	fragment,in
R5085	T7479	T7480	nummod	"1,416",bp
R5086	T7480	T7478	compound	bp,fragment
R5087	T7481	T7480	punct	-,bp
R5088	T7482	T7436	punct	.,results
R5089	T7484	T7485	punct	(,E
R509	T843	T839	acl	resulting,Alterations
R5090	T7485	T7486	meta	E,analysis
R5091	T7487	T7485	punct	),E
R5092	T7488	T7489	compound	Northern,blot
R5093	T7489	T7486	compound	blot,analysis
R5094	T7490	T7486	prep	of,analysis
R5095	T7491	T7492	amod	total,RNA
R5096	T7492	T7490	pobj	RNA,of
R5097	T7493	T7492	acl	isolated,RNA
R5098	T7494	T7493	prep	from,isolated
R5099	T7495	T7494	pobj	testis,from
R51	T140	T137	pobj	difficulty,because
R510	T844	T843	prep	in,resulting
R5100	T7496	T7495	prep	of,testis
R5101	T7497	T7498	amod	homozygous,wt
R5102	T7498	T7499	nmod	wt,mice
R5103	T7499	T7496	pobj	mice,of
R5104	T7500	T7498	cc	and,wt
R5105	T7501	T7502	compound	XpdTTD,TTD
R5106	T7502	T7498	conj	TTD,wt
R5107	T7503	T7502	punct	/,TTD
R5108	T7504	T7498	punct	", ",wt
R5109	T7505	T7506	amod	heterozygous,wt
R511	T845	T846	amod	defective,function
R5110	T7506	T7498	conj	wt,wt
R5111	T7507	T7506	compound	Xpd†XPCS,wt
R5112	T7508	T7506	punct	/,wt
R5113	T7509	T7506	cc	and,wt
R5114	T7510	T7511	compound	XpdTTD,wt
R5115	T7511	T7506	conj	wt,wt
R5116	T7512	T7511	punct	/,wt
R5117	T7513	T7506	punct	", ",wt
R5118	T7514	T7506	cc	and,wt
R5119	T7515	T7516	amod	compound,TTD
R512	T846	T844	pobj	function,in
R5120	T7516	T7506	conj	TTD,wt
R5121	T7517	T7516	amod	heterozygous,TTD
R5122	T7518	T7516	compound	Xpd†XPCS,TTD
R5123	T7519	T7516	punct	/,TTD
R5124	T7520	T7521	mark	as,indicated
R5125	T7521	T7493	advcl	indicated,isolated
R5126	T7522	T7486	punct	.,analysis
R5127	T7524	T7525	nsubj	Hybridisation,detects
R5128	T7526	T7524	prep	with,Hybridisation
R5129	T7527	T7528	det	a,probe
R513	T847	T846	compound	TFIIH,function
R5130	T7528	T7526	pobj	probe,with
R5131	T7529	T7530	nummod	1.4,kb
R5132	T7530	T7528	compound	kb,probe
R5133	T7531	T7530	punct	-,kb
R5134	T7532	T7528	compound	mouse,probe
R5135	T7533	T7528	compound	Xpd,probe
R5136	T7534	T7528	compound	cDNA,probe
R5137	T7535	T7525	dobj	mRNAs,detects
R5138	T7536	T7535	prep	of,mRNAs
R5139	T7537	T7538	nummod	4,kb
R514	T848	T840	auxpass	are,associated
R5140	T7538	T7536	pobj	kb,of
R5141	T7539	T7537	punct	", ",4
R5142	T7540	T7537	conj	3.3,4
R5143	T7541	T7540	punct	", ",3.3
R5144	T7542	T7540	cc	and,3.3
R5145	T7543	T7540	conj	2.7,3.3
R5146	T7544	T7535	prep	from,mRNAs
R5147	T7545	T7546	nmod	wt,alleles
R5148	T7546	T7544	pobj	alleles,from
R5149	T7547	T7545	punct	", ",wt
R515	T849	T840	prep	with,associated
R5150	T7548	T7545	conj	Xpd†XPCS,wt
R5151	T7549	T7548	punct	", ",Xpd†XPCS
R5152	T7550	T7548	cc	and,Xpd†XPCS
R5153	T7551	T7548	conj	XpdTTD,Xpd†XPCS
R5154	T7552	T7535	punct	", ",mRNAs
R5155	T7553	T7535	advmod	respectively,mRNAs
R5156	T7554	T7525	punct	.,detects
R5157	T7556	T7557	det	An,gel
R5158	T7557	T7565	nsubjpass	gel,shown
R5159	T7558	T7559	compound	ethidium,bromide
R516	T850	T851	npadvmod	UV,sensitive
R5160	T7559	T7560	npadvmod	bromide,stained
R5161	T7560	T7557	amod	stained,gel
R5162	T7561	T7559	punct	(,bromide
R5163	T7562	T7559	appos	EtBr,bromide
R5164	T7563	T7560	punct	),stained
R5165	T7564	T7560	punct	–,stained
R5166	T7566	T7557	acl	showing,gel
R5167	T7567	T7568	det	the,amount
R5168	T7568	T7566	dobj	amount,showing
R5169	T7569	T7568	prep	of,amount
R517	T851	T853	amod	sensitive,disorders
R5170	T7570	T7571	amod	total,RNA
R5171	T7571	T7569	pobj	RNA,of
R5172	T7572	T7571	acl	loaded,RNA
R5173	T7573	T7565	auxpass	is,shown
R5174	T7574	T7565	advmod	below,shown
R5175	T7575	T7565	punct	.,shown
R5176	T7658	T7659	amod	Partial,Rescue
R5177	T7660	T7659	prep	of,Rescue
R5178	T7661	T7660	pobj	TTD,of
R5179	T7662	T7661	amod	Cutaneous,TTD
R518	T852	T851	punct	-,sensitive
R5180	T7663	T7661	punct	", ",TTD
R5181	T7664	T7661	conj	Blood,TTD
R5182	T7665	T7664	punct	", ",Blood
R5183	T7666	T7664	cc	and,Blood
R5184	T7667	T7668	amod	Developmental,Phenotypes
R5185	T7668	T7664	conj	Phenotypes,Blood
R5186	T7669	T7659	prep	in,Rescue
R5187	T7670	T7671	nmod	Compound,Mice
R5188	T7671	T7669	pobj	Mice,in
R5189	T7672	T7671	amod	Heterozygous,Mice
R519	T853	T849	pobj	disorders,with
R5190	T7673	T7674	compound	XpdTTD,†XPCS
R5191	T7674	T7671	compound	†XPCS,Mice
R5192	T7675	T7674	punct	/,†XPCS
R5193	T7677	T7678	punct	(,A
R5194	T7678	T7679	meta	A,Photographs
R5195	T7680	T7678	punct	),A
R5196	T7681	T7679	prep	of,Photographs
R5197	T7682	T7683	nummod	5,mo
R5198	T7683	T7685	npadvmod	mo,old
R5199	T7684	T7683	punct	-,mo
R52	T141	T140	amod	inherent,difficulty
R520	T854	T853	punct	", ",disorders
R5200	T7685	T7687	amod	old,mice
R5201	T7686	T7685	punct	-,old
R5202	T7687	T7681	pobj	mice,of
R5203	T7688	T7689	amod	homozygous,TTD
R5204	T7689	T7687	nmod	TTD,mice
R5205	T7690	T7689	nmod	XpdTTD,TTD
R5206	T7691	T7689	punct	/,TTD
R5207	T7692	T7689	punct	", ",TTD
R5208	T7693	T7694	nmod	compound,†XPCS
R5209	T7694	T7689	conj	†XPCS,TTD
R521	T855	T853	amod	multisystem,disorders
R5210	T7695	T7694	amod	heterozygous,†XPCS
R5211	T7696	T7694	compound	XpdTTD,†XPCS
R5212	T7697	T7694	punct	/,†XPCS
R5213	T7698	T7694	punct	", ",†XPCS
R5214	T7699	T7694	cc	and,†XPCS
R5215	T7700	T7694	conj	wt,†XPCS
R5216	T7701	T7679	punct	.,Photographs
R5217	T7704	T7703	punct	: ,Insets
R5218	T7705	T7703	appos	images,Insets
R5219	T7706	T7705	prep	of,images
R522	T856	T853	prep	including,disorders
R5220	T7707	T7708	amod	first,round
R5221	T7708	T7710	compound	round,loss
R5222	T7709	T7708	punct	-,round
R5223	T7710	T7706	pobj	loss,of
R5224	T7711	T7710	compound	hair,loss
R5225	T7712	T7703	punct	.,Insets
R5226	T7714	T7715	punct	(,B
R5227	T7715	T7716	meta	B,analysis
R5228	T7717	T7715	punct	),B
R5229	T7718	T7716	amod	Histological,analysis
R523	T857	T858	compound	xeroderma,pigmentosum
R5230	T7719	T7716	prep	of,analysis
R5231	T7720	T7721	det	the,skin
R5232	T7721	T7719	pobj	skin,of
R5233	T7722	T7721	prep	of,skin
R5234	T7723	T7724	nmod	XpdTTD,TTD
R5235	T7724	T7726	nmod	TTD,mice
R5236	T7725	T7724	punct	/,TTD
R5237	T7726	T7722	pobj	mice,of
R5238	T7727	T7724	punct	", ",TTD
R5239	T7728	T7729	compound	XpdTTD,†XPCS
R524	T858	T856	pobj	pigmentosum,including
R5240	T7729	T7724	conj	†XPCS,TTD
R5241	T7730	T7729	punct	/,†XPCS
R5242	T7731	T7729	punct	", ",†XPCS
R5243	T7732	T7729	cc	and,†XPCS
R5244	T7733	T7729	conj	wt,†XPCS
R5245	T7734	T7716	punct	.,analysis
R5246	T7736	T7737	npadvmod	TTD,associated
R5247	T7737	T7739	amod	associated,acanthosis
R5248	T7738	T7737	punct	-,associated
R5249	T7739	T7740	nsubj	acanthosis,were
R525	T859	T858	punct	(,pigmentosum
R5250	T7741	T7742	punct	(,epidermis
R5251	T7742	T7739	parataxis	epidermis,acanthosis
R5252	T7743	T7742	amod	thicker,epidermis
R5253	T7744	T7742	punct	", ",epidermis
R5254	T7745	T7742	acl	indicated,epidermis
R5255	T7746	T7745	agent	by,indicated
R5256	T7747	T7748	amod	solid,line
R5257	T7748	T7746	pobj	line,by
R5258	T7749	T7748	amod	vertical,line
R5259	T7750	T7742	punct	),epidermis
R526	T860	T858	appos	XP,pigmentosum
R5260	T7751	T7739	punct	", ",acanthosis
R5261	T7752	T7753	amod	pronounced,layer
R5262	T7753	T7739	conj	layer,acanthosis
R5263	T7754	T7753	amod	granular,layer
R5264	T7755	T7753	punct	(,layer
R5265	T7756	T7753	acl	indicated,layer
R5266	T7757	T7756	agent	by,indicated
R5267	T7758	T7757	pobj	arrows,by
R5268	T7759	T7753	punct	),layer
R5269	T7760	T7753	punct	", ",layer
R527	T861	T858	punct	),pigmentosum
R5270	T7761	T7753	cc	and,layer
R5271	T7762	T7763	amod	sebacious,hyperplasia
R5272	T7763	T7753	conj	hyperplasia,layer
R5273	T7764	T7763	compound	gland,hyperplasia
R5274	T7765	T7763	punct	(,hyperplasia
R5275	T7766	T7763	acl	indicated,hyperplasia
R5276	T7767	T7766	agent	by,indicated
R5277	T7768	T7769	amod	dotted,line
R5278	T7769	T7767	pobj	line,by
R5279	T7770	T7769	amod	vertical,line
R528	T862	T858	punct	", ",pigmentosum
R5280	T7771	T7740	punct	),were
R5281	T7772	T7740	acomp	absent,were
R5282	T7773	T7740	prep	in,were
R5283	T7774	T7775	det	the,epidermis
R5284	T7775	T7773	pobj	epidermis,in
R5285	T7776	T7775	prep	of,epidermis
R5286	T7777	T7778	nmod	XpdTTD,†XPCS
R5287	T7778	T7780	nmod	†XPCS,mice
R5288	T7779	T7778	punct	/,†XPCS
R5289	T7780	T7776	pobj	mice,of
R529	T863	T858	conj	XP,pigmentosum
R5290	T7781	T7778	cc	and,†XPCS
R5291	T7782	T7778	conj	wt,†XPCS
R5292	T7783	T7740	punct	.,were
R5293	T7786	T7785	appos	400,Magnification
R5294	T7787	T7786	punct	×,400
R5295	T7788	T7785	punct	.,Magnification
R5296	T7790	T7791	punct	(,C
R5297	T7791	T7792	meta	C,content
R5298	T7793	T7791	punct	),C
R5299	T7794	T7792	compound	Cysteine,content
R53	T142	T140	prep	in,difficulty
R530	T864	T863	acl	combined,XP
R5300	T7795	T7792	prep	of,content
R5301	T7796	T7795	pobj	hair,of
R5302	T7797	T7796	prep	from,hair
R5303	T7798	T7799	nmod	wt,mice
R5304	T7799	T7797	pobj	mice,from
R5305	T7800	T7798	punct	", ",wt
R5306	T7801	T7802	compound	XpdTTD,TTD
R5307	T7802	T7798	conj	TTD,wt
R5308	T7803	T7802	punct	/,TTD
R5309	T7804	T7802	punct	", ",TTD
R531	T865	T864	prep	with,combined
R5310	T7805	T7802	cc	and,TTD
R5311	T7806	T7807	compound	XpdTTD,†XPCS
R5312	T7807	T7802	conj	†XPCS,TTD
R5313	T7808	T7807	punct	/,†XPCS
R5314	T7809	T7792	punct	.,content
R5315	T7811	T7812	det	The,value
R5316	T7812	T7815	nsubj	value,indicates
R5317	T7813	T7812	compound	p,value
R5318	T7814	T7812	punct	-,value
R5319	T7816	T7817	amod	significant,differences
R532	T866	T867	compound	Cockayne,syndrome
R5320	T7817	T7815	dobj	differences,indicates
R5321	T7818	T7817	prep	between,differences
R5322	T7819	T7818	pobj	mutants,between
R5323	T7820	T7819	cc	and,mutants
R5324	T7821	T7819	conj	wt,mutants
R5325	T7822	T7818	punct	", ",between
R5326	T7823	T7824	advmod	as,as
R5327	T7824	T7818	cc	as,between
R5328	T7825	T7824	advmod	well,as
R5329	T7826	T7818	conj	between,between
R533	T867	T865	pobj	syndrome,with
R5330	T7827	T7828	nmod	XpdTTD,TTD
R5331	T7828	T7830	nmod	TTD,mice
R5332	T7829	T7828	punct	/,TTD
R5333	T7830	T7826	pobj	mice,between
R5334	T7831	T7828	cc	and,TTD
R5335	T7832	T7833	compound	XpdTTD,†XPCS
R5336	T7833	T7828	conj	†XPCS,TTD
R5337	T7834	T7833	punct	/,†XPCS
R5338	T7835	T7815	punct	.,indicates
R5339	T7837	T7838	compound	Error,bars
R534	T868	T867	punct	(,syndrome
R5340	T7838	T7839	nsubj	bars,indicate
R5341	T7840	T7841	amod	standard,error
R5342	T7841	T7839	dobj	error,indicate
R5343	T7842	T7841	prep	of,error
R5344	T7843	T7844	det	the,mean
R5345	T7844	T7842	pobj	mean,of
R5346	T7845	T7841	punct	(,error
R5347	T7846	T7841	appos	SEM,error
R5348	T7847	T7839	punct	),indicate
R5349	T7848	T7839	punct	.,indicate
R535	T869	T867	appos	CS,syndrome
R5350	T7850	T7851	punct	(,D
R5351	T7851	T7852	meta	D,values
R5352	T7853	T7851	punct	),D
R5353	T7854	T7852	compound	Hematocrit,values
R5354	T7855	T7852	prep	from,values
R5355	T7856	T7855	pobj	blood,from
R5356	T7857	T7856	prep	of,blood
R5357	T7858	T7859	nmod	XpdTTD,TTD
R5358	T7859	T7861	nmod	TTD,mice
R5359	T7860	T7859	punct	/,TTD
R536	T870	T863	punct	),XP
R5360	T7861	T7857	pobj	mice,of
R5361	T7862	T7859	cc	and,TTD
R5362	T7863	T7864	compound	XpdTTD,†XPCS
R5363	T7864	T7859	conj	†XPCS,TTD
R5364	T7865	T7864	punct	/,†XPCS
R5365	T7866	T7852	punct	.,values
R5366	T7868	T7869	det	The,values
R5367	T7869	T7872	nsubj	values,indicate
R5368	T7870	T7869	compound	p,values
R5369	T7871	T7869	punct	-,values
R537	T871	T863	punct	", ",XP
R5370	T7873	T7874	det	the,significance
R5371	T7874	T7872	dobj	significance,indicate
R5372	T7875	T7874	prep	of,significance
R5373	T7876	T7877	det	the,difference
R5374	T7877	T7875	pobj	difference,of
R5375	T7878	T7872	advcl	relative,indicate
R5376	T7879	T7878	prep	to,relative
R5377	T7880	T7879	pobj	wt,to
R5378	T7881	T7872	punct	.,indicate
R5379	T7883	T7884	compound	Error,bars
R538	T872	T863	cc	and,XP
R5380	T7884	T7885	nsubj	bars,indicate
R5381	T7886	T7885	dobj	SEM,indicate
R5382	T7887	T7885	punct	.,indicate
R5383	T7889	T7890	punct	(,E
R5384	T7890	T7891	meta	E,weights
R5385	T7892	T7890	punct	),E
R5386	T7893	T7891	compound	Body,weights
R5387	T7894	T7891	prep	of,weights
R5388	T7895	T7896	amod	developing,mice
R5389	T7896	T7894	pobj	mice,of
R539	T873	T863	conj	trichothiodystrophy,XP
R5390	T7897	T7898	nmod	XpdTTD,TTD
R5391	T7898	T7896	nmod	TTD,mice
R5392	T7899	T7898	punct	/,TTD
R5393	T7900	T7898	cc	and,TTD
R5394	T7901	T7902	compound	XpdTTD,†XPCS
R5395	T7902	T7898	conj	†XPCS,TTD
R5396	T7903	T7902	punct	/,†XPCS
R5397	T7904	T7896	prep	after,mice
R5398	T7905	T7904	pobj	weaning,after
R5399	T7906	T7891	acl	plotted,weights
R54	T143	T142	pcomp	distinguishing,in
R540	T874	T873	punct	(,trichothiodystrophy
R5400	T7907	T7906	prep	as,plotted
R5401	T7908	T7909	det	a,percentage
R5402	T7909	T7907	pobj	percentage,as
R5403	T7910	T7909	prep	of,percentage
R5404	T7911	T7912	det	the,weight
R5405	T7912	T7910	pobj	weight,of
R5406	T7913	T7912	prep	of,weight
R5407	T7914	T7915	npadvmod	age,matched
R5408	T7915	T7917	amod	matched,littermates
R5409	T7916	T7915	punct	-,matched
R541	T875	T873	appos	TTD,trichothiodystrophy
R5410	T7917	T7913	pobj	littermates,of
R5411	T7918	T7917	nmod	control,littermates
R5412	T7919	T7917	nmod	wt,littermates
R5413	T7920	T7919	cc	and,wt
R5414	T7921	T7919	conj	heterozygote,wt
R5415	T7922	T7923	punct	(,hz
R5416	T7923	T7921	parataxis	hz,heterozygote
R5417	T7924	T7923	punct	),hz
R5418	T7925	T7926	punct	(,set
R5419	T7926	T7909	parataxis	set,percentage
R542	T876	T840	punct	),associated
R5420	T7927	T7926	prep	at,set
R5421	T7928	T7929	nummod	100,%
R5422	T7929	T7927	pobj	%,at
R5423	T7930	T7926	punct	),set
R5424	T7931	T7891	punct	.,weights
R5425	T7933	T7934	compound	Error,bars
R5426	T7934	T7935	nsubj	bars,indicate
R5427	T7936	T7935	dobj	SEM,indicate
R5428	T7937	T7935	punct	.,indicate
R5429	T8042	T8041	prep	of,Rescue
R543	T877	T878	punct	[,8
R5430	T8043	T8044	npadvmod	TTD,Associated
R5431	T8044	T8046	amod	Associated,Features
R5432	T8045	T8044	punct	-,Associated
R5433	T8046	T8042	pobj	Features,of
R5434	T8047	T8046	amod	Segmental,Features
R5435	T8048	T8046	amod	Progeroid,Features
R5436	T8049	T8046	prep	in,Features
R5437	T8050	T8051	amod	Compound,Mice
R5438	T8051	T8049	pobj	Mice,in
R5439	T8052	T8051	amod	Heterozygous,Mice
R544	T878	T840	parataxis	8,associated
R5440	T8053	T8054	compound	Xpd TTD,†XPCS
R5441	T8054	T8051	compound	†XPCS,Mice
R5442	T8055	T8054	punct	/,†XPCS
R5443	T8057	T8058	punct	(,A
R5444	T8058	T8059	meta	A,Photographs
R5445	T8060	T8058	punct	),A
R5446	T8061	T8059	prep	of,Photographs
R5447	T8062	T8063	nummod	20,mo
R5448	T8063	T8065	npadvmod	mo,old
R5449	T8064	T8063	punct	-,mo
R545	T879	T880	punct	–,10
R5450	T8065	T8067	amod	old,mice
R5451	T8066	T8065	punct	-,old
R5452	T8067	T8061	pobj	mice,of
R5453	T8068	T8067	nmod	wt,mice
R5454	T8069	T8068	punct	", ",wt
R5455	T8070	T8071	amod	compound,†XPCS
R5456	T8071	T8068	conj	†XPCS,wt
R5457	T8072	T8071	amod	heterozygous,†XPCS
R5458	T8073	T8071	compound	XpdTTD,†XPCS
R5459	T8074	T8071	punct	/,†XPCS
R546	T880	T878	prep	10,8
R5460	T8075	T8071	punct	", ",†XPCS
R5461	T8076	T8071	cc	and,†XPCS
R5462	T8077	T8078	amod	homozygous,TTD
R5463	T8078	T8071	conj	TTD,†XPCS
R5464	T8079	T8078	compound	XpdTTD,TTD
R5465	T8080	T8078	punct	/,TTD
R5466	T8081	T8059	punct	.,Photographs
R5467	T8084	T8085	det	the,cachexia
R5468	T8085	T8083	dobj	cachexia,Note
R5469	T8086	T8085	amod	extreme,cachexia
R547	T881	T878	punct	],8
R5470	T8087	T8085	punct	(,cachexia
R5471	T8088	T8085	appos	lack,cachexia
R5472	T8089	T8088	prep	of,lack
R5473	T8090	T8091	amod	subcutaneous,fat
R5474	T8091	T8089	pobj	fat,of
R5475	T8092	T8085	punct	),cachexia
R5476	T8093	T8085	prep	in,cachexia
R5477	T8094	T8095	det	the,mouse
R5478	T8095	T8093	pobj	mouse,in
R5479	T8096	T8097	compound	XpdTTD,TTD
R548	T882	T840	punct	.,associated
R5480	T8097	T8095	compound	TTD,mouse
R5481	T8098	T8097	punct	/,TTD
R5482	T8099	T8083	cc	and,Note
R5483	T8100	T8101	det	the,absence
R5484	T8101	T8083	conj	absence,Note
R5485	T8102	T8101	prep	of,absence
R5486	T8103	T8104	det	this,phenotype
R5487	T8104	T8102	pobj	phenotype,of
R5488	T8105	T8101	prep	in,absence
R5489	T8106	T8107	nmod	wt,mice
R549	T884	T885	nsubjpass	XP,marked
R5490	T8107	T8105	pobj	mice,in
R5491	T8108	T8106	cc	and,wt
R5492	T8109	T8110	compound	XpdTTD,†XPCS
R5493	T8110	T8106	conj	†XPCS,wt
R5494	T8111	T8110	punct	/,†XPCS
R5495	T8112	T8083	punct	.,Note
R5496	T8114	T8115	punct	(,B
R5497	T8115	T8116	meta	B,Radiographs
R5498	T8117	T8115	punct	),B
R5499	T8118	T8116	prep	of,Radiographs
R55	T144	T145	amod	specific,effects
R550	T886	T885	auxpass	is,marked
R5500	T8119	T8120	nummod	20,mo
R5501	T8120	T8122	npadvmod	mo,old
R5502	T8121	T8120	punct	-,mo
R5503	T8122	T8124	amod	old,mice
R5504	T8123	T8122	punct	-,old
R5505	T8124	T8118	pobj	mice,of
R5506	T8125	T8124	amod	male,mice
R5507	T8126	T8124	nmod	wt,mice
R5508	T8127	T8126	punct	", ",wt
R5509	T8128	T8129	compound	XpdTTD,†XPCS
R551	T887	T885	agent	by,marked
R5510	T8129	T8126	conj	†XPCS,wt
R5511	T8130	T8129	punct	/,†XPCS
R5512	T8131	T8129	punct	", ",†XPCS
R5513	T8132	T8129	cc	and,†XPCS
R5514	T8133	T8134	compound	XpdTTD,TTD
R5515	T8134	T8129	conj	TTD,†XPCS
R5516	T8135	T8134	punct	/,TTD
R5517	T8136	T8116	punct	.,Radiographs
R5518	T8138	T8139	amod	Ageing,mice
R5519	T8139	T8143	nsubj	mice,develop
R552	T888	T889	npadvmod	sun,induced
R5520	T8140	T8141	compound	XpdTTD,TTD
R5521	T8141	T8139	compound	TTD,mice
R5522	T8142	T8141	punct	/,TTD
R5523	T8144	T8143	dobj	kyphosis,develop
R5524	T8145	T8144	punct	(,kyphosis
R5525	T8146	T8144	appos	curvature,kyphosis
R5526	T8147	T8146	prep	of,curvature
R5527	T8148	T8149	det	the,column
R5528	T8149	T8147	pobj	column,of
R5529	T8150	T8149	amod	spinal,column
R553	T889	T891	amod	induced,anomalies
R5530	T8151	T8144	punct	),kyphosis
R5531	T8152	T8144	cc	and,kyphosis
R5532	T8153	T8144	conj	reduction,kyphosis
R5533	T8154	T8153	prep	of,reduction
R5534	T8155	T8156	compound	bone,mineral
R5535	T8156	T8157	compound	mineral,density
R5536	T8157	T8154	pobj	density,of
R5537	T8158	T8159	mark	as,shown
R5538	T8159	T8143	advcl	shown,develop
R5539	T8160	T8159	prep	in,shown
R554	T890	T889	punct	-,induced
R5540	T8161	T8162	det	the,segment
R5541	T8162	T8160	pobj	segment,in
R5542	T8163	T8164	quantmod	6,8
R5543	T8164	T8162	nummod	8,segment
R5544	T8165	T8164	punct	–,8
R5545	T8166	T8162	prep	of,segment
R5546	T8167	T8168	det	the,vertebrae
R5547	T8168	T8166	pobj	vertebrae,of
R5548	T8169	T8168	compound	tail,vertebrae
R5549	T8170	T8162	acl	counted,segment
R555	T891	T887	pobj	anomalies,by
R5550	T8171	T8170	prep	from,counted
R5551	T8172	T8173	det	the,pelvis
R5552	T8173	T8171	pobj	pelvis,from
R5553	T8174	T8175	punct	(,see
R5554	T8175	T8143	parataxis	see,develop
R5555	T8176	T8175	dobj	close,see
R5556	T8177	T8176	punct	-,close
R5557	T8178	T8176	prt	up,close
R5558	T8179	T8176	prep	at,close
R5559	T8180	T8179	pobj	right,at
R556	T892	T891	compound	pigmentation,anomalies
R5560	T8181	T8175	punct	),see
R5561	T8182	T8143	punct	.,develop
R5562	T8185	T8186	det	the,absence
R5563	T8186	T8184	dobj	absence,Note
R5564	T8187	T8186	prep	of,absence
R5565	T8188	T8189	det	these,features
R5566	T8189	T8187	pobj	features,of
R5567	T8190	T8186	prep	in,absence
R5568	T8191	T8192	det	the,mouse
R5569	T8192	T8190	pobj	mouse,in
R557	T893	T891	cc	and,anomalies
R5570	T8193	T8194	compound	XpdTTD , † XPCS
R5571	T8194	T8192	compound	† XPCS,mouse
R5572	T8195	T8194	punct	/, † XPCS
R5573	T8196	T8184	punct	.,Note
R5574	T8198	T8199	punct	(,C
R5575	T8199	T8200	meta	C,Quantification
R5576	T8201	T8199	punct	),C
R5577	T8202	T8200	prep	of,Quantification
R5578	T8203	T8204	amod	relative,density
R5579	T8204	T8202	pobj	density,of
R558	T894	T895	det	a,elevation
R5580	T8205	T8206	compound	bone,mineral
R5581	T8206	T8204	compound	mineral,density
R5582	T8207	T8204	prep	of,density
R5583	T8208	T8209	compound	tail,vertebrae
R5584	T8209	T8207	pobj	vertebrae,of
R5585	T8210	T8209	prep	from,vertebrae
R5586	T8211	T8212	nummod	20,mo
R5587	T8212	T8214	npadvmod	mo,old
R5588	T8213	T8212	punct	-,mo
R5589	T8214	T8216	amod	old,mice
R559	T895	T891	conj	elevation,anomalies
R5590	T8215	T8214	punct	-,old
R5591	T8216	T8210	pobj	mice,from
R5592	T8217	T8216	amod	male,mice
R5593	T8218	T8216	nmod	wt,mice
R5594	T8219	T8220	punct	(,3
R5595	T8220	T8218	parataxis	3,wt
R5596	T8221	T8220	nsubj	n,3
R5597	T8222	T8220	punct	=,3
R5598	T8223	T8220	punct	),3
R5599	T8224	T8218	punct	", ",wt
R56	T145	T143	dobj	effects,distinguishing
R560	T896	T897	amod	greater,"1,000"
R5600	T8225	T8226	compound	XpdTTD,†XPCS
R5601	T8226	T8218	conj	†XPCS,wt
R5602	T8227	T8226	punct	/,†XPCS
R5603	T8228	T8229	punct	(,4
R5604	T8229	T8226	parataxis	4,†XPCS
R5605	T8230	T8229	nsubj	n,4
R5606	T8231	T8229	punct	=,4
R5607	T8232	T8229	punct	),4
R5608	T8233	T8226	punct	", ",†XPCS
R5609	T8234	T8226	cc	and,†XPCS
R561	T897	T899	quantmod	"1,000",fold
R5610	T8235	T8236	compound	XpdTTD,TTD
R5611	T8236	T8226	conj	TTD,†XPCS
R5612	T8237	T8236	punct	/,TTD
R5613	T8238	T8239	punct	(,3
R5614	T8239	T8236	parataxis	3,TTD
R5615	T8240	T8239	nsubj	n,3
R5616	T8241	T8239	punct	=,3
R5617	T8242	T8239	punct	),3
R5618	T8243	T8200	punct	.,Quantification
R5619	T8245	T8246	det	The,values
R562	T898	T897	quantmod	than,"1,000"
R5620	T8246	T8249	nsubj	values,indicate
R5621	T8247	T8246	compound	p,values
R5622	T8248	T8246	punct	-,values
R5623	T8250	T8251	det	the,significance
R5624	T8251	T8249	dobj	significance,indicate
R5625	T8252	T8251	prep	of,significance
R5626	T8253	T8254	det	the,difference
R5627	T8254	T8252	pobj	difference,of
R5628	T8255	T8249	advcl	relative,indicate
R5629	T8256	T8255	prep	to,relative
R563	T899	T895	nummod	fold,elevation
R5630	T8257	T8258	compound	XpdTTD,TTD
R5631	T8258	T8256	pobj	TTD,to
R5632	T8259	T8258	punct	/,TTD
R5633	T8260	T8249	punct	.,indicate
R5634	T8262	T8263	compound	Error,bars
R5635	T8263	T8264	nsubj	bars,indicate
R5636	T8265	T8264	dobj	SEM,indicate
R5637	T8266	T8264	punct	.,indicate
R5638	T8268	T8269	punct	(,D
R5639	T8269	T8270	meta	D,curves
R564	T900	T899	punct	-,fold
R5640	T8271	T8269	punct	),D
R5641	T8272	T8273	compound	Body,weight
R5642	T8273	T8270	compound	weight,curves
R5643	T8274	T8270	prep	as,curves
R5644	T8275	T8276	det	a,function
R5645	T8276	T8274	pobj	function,as
R5646	T8277	T8276	prep	of,function
R5647	T8278	T8277	pobj	time,of
R5648	T8279	T8270	punct	.,curves
R5649	T8282	T8283	mark	that,rescued
R565	T901	T895	prep	in,elevation
R5650	T8283	T8281	ccomp	rescued,Note
R5651	T8284	T8285	det	the,cachexia
R5652	T8285	T8283	nsubjpass	cachexia,rescued
R5653	T8286	T8287	npadvmod	age,dependent
R5654	T8287	T8285	amod	dependent,cachexia
R5655	T8288	T8287	punct	-,dependent
R5656	T8289	T8285	acl	observed,cachexia
R5657	T8290	T8289	prep	in,observed
R5658	T8291	T8292	compound	XpdTTD,TTD
R5659	T8292	T8294	compound	TTD,mice
R566	T902	T903	compound	skin,cancer
R5660	T8293	T8292	punct	/,TTD
R5661	T8294	T8290	pobj	mice,in
R5662	T8295	T8283	auxpass	was,rescued
R5663	T8296	T8283	prep	in,rescued
R5664	T8297	T8298	preconj	both,male
R5665	T8298	T8299	nmod	male,mice
R5666	T8299	T8296	pobj	mice,in
R5667	T8300	T8298	cc	and,male
R5668	T8301	T8298	conj	female,male
R5669	T8302	T8303	compound	XpdTTD , †XPCS
R567	T903	T904	compound	cancer,risk
R5670	T8303	T8299	compound	†XPCS,mice
R5671	T8304	T8303	punct	/, †XPCS
R5672	T8305	T8281	punct	.,Note
R5673	T8307	T8308	amod	Significant,differences
R5674	T8308	T8309	nsubjpass	differences,observed
R5675	T8310	T8308	prep	between,differences
R5676	T8311	T8310	pobj	wt,between
R5677	T8312	T8311	cc	and,wt
R5678	T8313	T8314	compound	XpdTTD,TTD
R5679	T8314	T8311	conj	TTD,wt
R568	T904	T901	pobj	risk,in
R5680	T8315	T8314	punct	/,TTD
R5681	T8316	T8310	cc	but,between
R5682	T8317	T8316	neg	not,but
R5683	T8318	T8310	conj	between,between
R5684	T8319	T8320	nmod	wt,mice
R5685	T8320	T8318	pobj	mice,between
R5686	T8321	T8319	cc	and,wt
R5687	T8322	T8323	compound	XpdTTD,†XPCS
R5688	T8323	T8319	conj	†XPCS,wt
R5689	T8324	T8323	punct	/,†XPCS
R569	T905	T885	punct	.,marked
R5690	T8325	T8309	auxpass	were,observed
R5691	T8326	T8309	prep	at,observed
R5692	T8327	T8328	nummod	9,mo
R5693	T8328	T8326	pobj	mo,at
R5694	T8329	T8327	cc	and,9
R5695	T8330	T8327	conj	18,9
R5696	T8331	T8328	prep	of,mo
R5697	T8332	T8331	pobj	age,of
R5698	T8333	T8334	mark	as,indicated
R5699	T8334	T8309	advcl	indicated,observed
R57	T146	T145	amod	biallelic,effects
R570	T907	T908	amod	Severe,cases
R5700	T8335	T8334	agent	by,indicated
R5701	T8336	T8335	pobj	asterisks,by
R5702	T8337	T8309	punct	.,observed
R5703	T8339	T8340	compound	Error,bars
R5704	T8340	T8341	nsubj	bars,indicate
R5705	T8342	T8341	dobj	SEM,indicate
R5706	T8343	T8341	punct	.,indicate
R5707	T8564	T8565	compound	TFIIH,Functions
R5708	T8566	T8565	cc	and,Functions
R5709	T8567	T8565	conj	Mechanisms,Functions
R571	T908	T909	nsubj	cases,present
R5710	T8568	T8567	prep	of,Mechanisms
R5711	T8569	T8570	npadvmod	XPD,Associated
R5712	T8570	T8572	amod	Associated,Pleiotropy
R5713	T8571	T8570	punct	-,Associated
R5714	T8572	T8568	pobj	Pleiotropy,of
R5715	T8573	T8572	compound	Disease,Pleiotropy
R5716	T8575	T8576	punct	(,A
R5717	T8576	T8577	meta	A,survival
R5718	T8578	T8576	punct	),A
R5719	T8579	T8577	amod	Cellular,survival
R572	T910	T909	aux	can,present
R5720	T8580	T8577	prep	after,survival
R5721	T8581	T8582	compound	UV,irradiation
R5722	T8582	T8580	pobj	irradiation,after
R5723	T8583	T8577	punct	.,survival
R5724	T8585	T8586	nsubjpass	Rescue,illustrated
R5725	T8587	T8585	prep	of,Rescue
R5726	T8588	T8589	amod	hemizygous,survival
R5727	T8589	T8587	pobj	survival,of
R5728	T8590	T8591	compound	XpdTTD,KO
R5729	T8591	T8589	compound	KO,survival
R573	T911	T909	advmod	also,present
R5730	T8592	T8591	punct	/,KO
R5731	T8593	T8585	prep	by,Rescue
R5732	T8594	T8595	nmod	Xpd†XPCS,alleles
R5733	T8595	T8593	pobj	alleles,by
R5734	T8596	T8594	cc	and,Xpd†XPCS
R5735	T8597	T8594	conj	Xpd†XP,Xpd†XPCS
R5736	T8598	T8586	auxpass	is,illustrated
R5737	T8599	T8586	agent	by,illustrated
R5738	T8600	T8599	pobj	arrows,by
R5739	T8601	T8600	acl	marked,arrows
R574	T912	T909	prep	with,present
R5740	T8602	T8601	oprd	A,marked
R5741	T8603	T8602	cc	and,A
R5742	T8604	T8602	conj	B,A
R5743	T8605	T8601	punct	", ",marked
R5744	T8606	T8601	advmod	respectively,marked
R5745	T8607	T8586	punct	.,illustrated
R5746	T8609	T8610	compound	UV,survival
R5747	T8610	T8611	nsubjpass	survival,depicted
R5748	T8612	T8610	prep	of,survival
R5749	T8613	T8614	amod	homozygous,cells
R575	T913	T914	compound	growth,retardation
R5750	T8614	T8612	pobj	cells,of
R5751	T8615	T8616	compound	XpdXPCS,XPCS
R5752	T8616	T8614	compound	XPCS,cells
R5753	T8617	T8616	punct	/,XPCS
R5754	T8618	T8619	punct	(,asterisk
R5755	T8619	T8614	parataxis	asterisk,cells
R5756	T8620	T8619	punct	),asterisk
R5757	T8621	T8614	prep	from,cells
R5758	T8622	T8623	det	the,allele
R5759	T8623	T8621	pobj	allele,from
R576	T914	T912	pobj	retardation,with
R5760	T8624	T8625	advmod	normally,expressed
R5761	T8625	T8623	amod	expressed,allele
R5762	T8626	T8623	amod	viable,allele
R5763	T8627	T8628	punct	(,XpdXPCS
R5764	T8628	T8623	parataxis	XpdXPCS,allele
R5765	T8629	T8628	punct	),XpdXPCS
R5766	T8630	T8611	auxpass	is,depicted
R5767	T8631	T8611	prep	by,depicted
R5768	T8632	T8633	det	a,line
R5769	T8633	T8631	pobj	line,by
R577	T915	T914	cc	and,retardation
R5770	T8634	T8633	amod	dotted,line
R5771	T8635	T8611	punct	.,depicted
R5772	T8637	T8638	compound	Survival,curves
R5773	T8638	T8639	nsubj	curves,represent
R5774	T8639	T8640	ccomp	represent,included
R5775	T8641	T8642	det	an,average
R5776	T8642	T8639	dobj	average,represent
R5777	T8643	T8642	prep	of,average
R5778	T8644	T8645	nummod	four,experiments
R5779	T8645	T8643	pobj	experiments,of
R578	T916	T917	amod	primary,neurodegeneration
R5780	T8646	T8645	amod	independent,experiments
R5781	T8647	T8640	punct	;,included
R5782	T8648	T8649	quantmod	1,2
R5783	T8649	T8651	nummod	2,lines
R5784	T8650	T8649	punct	–,2
R5785	T8651	T8640	nsubjpass	lines,included
R5786	T8652	T8651	compound	cell,lines
R5787	T8653	T8651	prep	per,lines
R5788	T8654	T8653	pobj	genotype,per
R5789	T8655	T8640	auxpass	were,included
R579	T917	T914	conj	neurodegeneration,retardation
R5790	T8656	T8640	prep	in,included
R5791	T8657	T8658	det	each,experiment
R5792	T8658	T8656	pobj	experiment,in
R5793	T8659	T8640	punct	.,included
R5794	T8661	T8662	compound	Error,bars
R5795	T8662	T8663	nsubj	bars,indicate
R5796	T8664	T8663	dobj	SEM,indicate
R5797	T8665	T8664	prep	between,SEM
R5798	T8666	T8665	pobj	experiments,between
R5799	T8667	T8663	punct	.,indicate
R58	T147	T143	prep	from,distinguishing
R580	T918	T919	punct	[,11
R5800	T8669	T8670	punct	(,B
R5801	T8670	T8671	meta	B,UDS
R5802	T8672	T8670	punct	),B
R5803	T8673	T8671	compound	UV,UDS
R5804	T8674	T8671	punct	-,UDS
R5805	T8675	T8671	punct	", ",UDS
R5806	T8676	T8677	det	a,measure
R5807	T8677	T8671	appos	measure,UDS
R5808	T8678	T8677	prep	of,measure
R5809	T8679	T8680	amod	global,repair
R581	T919	T909	parataxis	11,present
R5810	T8680	T8678	pobj	repair,of
R5811	T8681	T8680	compound	genome,repair
R5812	T8682	T8671	punct	.,UDS
R5813	T8684	T8685	dep	Number,included
R5814	T8686	T8684	prep	of,Number
R5815	T8687	T8686	pobj	experiments,of
R5816	T8688	T8685	punct	: ,included
R5817	T8689	T8690	nsubj	n,15
R5818	T8690	T8685	ccomp	15,included
R5819	T8691	T8690	punct	=,15
R582	T920	T919	punct	],11
R5820	T8692	T8693	punct	(,XpdTTD
R5821	T8693	T8690	parataxis	XpdTTD,15
R5822	T8694	T8693	punct	/,XpdTTD
R5823	T8695	T8693	dep	TTD,XpdTTD
R5824	T8696	T8693	punct	),XpdTTD
R5825	T8697	T8685	punct	", ",included
R5826	T8698	T8699	nsubj	n,6
R5827	T8699	T8685	ccomp	6,included
R5828	T8700	T8699	punct	=,6
R5829	T8701	T8702	punct	(,KO
R583	T921	T909	punct	.,present
R5830	T8702	T8699	parataxis	KO,6
R5831	T8703	T8702	compound	XpdTTD,KO
R5832	T8704	T8702	punct	/,KO
R5833	T8705	T8702	punct	),KO
R5834	T8706	T8685	punct	", ",included
R5835	T8707	T8708	nsubj	n,4
R5836	T8708	T8685	ccomp	4,included
R5837	T8709	T8708	punct	=,4
R5838	T8710	T8711	punct	(,†XPCS
R5839	T8711	T8708	parataxis	†XPCS,4
R584	T923	T924	nsubj	CS,are
R5840	T8712	T8711	compound	XpdTTD,†XPCS
R5841	T8713	T8711	punct	/,†XPCS
R5842	T8714	T8711	punct	),†XPCS
R5843	T8715	T8685	punct	", ",included
R5844	T8716	T8717	nsubj	n,2
R5845	T8717	T8685	ccomp	2,included
R5846	T8718	T8717	punct	=,2
R5847	T8719	T8720	punct	(,†XP
R5848	T8720	T8717	parataxis	†XP,2
R5849	T8721	T8720	compound	XpdTTD,†XP
R585	T925	T923	cc	and,CS
R5850	T8722	T8720	punct	/,†XP
R5851	T8723	T8720	punct	),†XP
R5852	T8724	T8685	punct	;,included
R5853	T8725	T8726	quantmod	1,2
R5854	T8726	T8728	nummod	2,lines
R5855	T8727	T8726	punct	–,2
R5856	T8728	T8685	nsubjpass	lines,included
R5857	T8729	T8728	compound	cell,lines
R5858	T8730	T8728	prep	per,lines
R5859	T8731	T8730	pobj	genotype,per
R586	T926	T923	conj	TTD,CS
R5860	T8732	T8685	auxpass	were,included
R5861	T8733	T8685	prep	in,included
R5862	T8734	T8735	det	each,experiment
R5863	T8735	T8733	pobj	experiment,in
R5864	T8736	T8685	punct	.,included
R5865	T8738	T8739	det	The,asterisk
R5866	T8739	T8740	nsubj	asterisk,indicates
R5867	T8740	T8741	ccomp	indicates,indicate
R5868	T8742	T8743	amod	significant,difference
R5869	T8743	T8740	dobj	difference,indicates
R587	T927	T924	punct	", ",are
R5870	T8744	T8743	prep	with,difference
R5871	T8745	T8746	compound	XpdTTD,TTD
R5872	T8746	T8744	pobj	TTD,with
R5873	T8747	T8746	punct	/,TTD
R5874	T8748	T8741	punct	;,indicate
R5875	T8749	T8741	nsubj	crosses,indicate
R5876	T8750	T8751	amod	significant,differences
R5877	T8751	T8741	dobj	differences,indicate
R5878	T8752	T8751	prep	with,differences
R5879	T8753	T8754	compound	XpdTTD,KO
R588	T928	T924	prep	on,are
R5880	T8754	T8752	pobj	KO,with
R5881	T8755	T8754	punct	/,KO
R5882	T8756	T8741	punct	.,indicate
R5883	T8758	T8759	punct	(,C
R5884	T8759	T8760	meta	C,RRS
R5885	T8761	T8759	punct	),C
R5886	T8762	T8760	compound	UV,RRS
R5887	T8763	T8760	punct	-,RRS
R5888	T8764	T8760	punct	", ",RRS
R5889	T8765	T8766	det	a,measure
R589	T929	T930	det	the,hand
R5890	T8766	T8760	appos	measure,RRS
R5891	T8767	T8766	prep	of,measure
R5892	T8768	T8769	npadvmod	transcription,coupled
R5893	T8769	T8771	amod	coupled,repair
R5894	T8770	T8769	punct	-,coupled
R5895	T8771	T8767	pobj	repair,of
R5896	T8772	T8771	prep	of,repair
R5897	T8773	T8774	npadvmod	UV,induced
R5898	T8774	T8776	amod	induced,lesions
R5899	T8775	T8774	punct	-,induced
R59	T148	T147	pobj	differences,from
R590	T930	T928	pobj	hand,on
R5900	T8776	T8772	pobj	lesions,of
R5901	T8777	T8760	punct	.,RRS
R5902	T8779	T8780	dep	Number,included
R5903	T8781	T8779	prep	of,Number
R5904	T8782	T8781	pobj	experiments,of
R5905	T8783	T8780	punct	: ,included
R5906	T8784	T8785	nsubj	n,7
R5907	T8785	T8780	ccomp	7,included
R5908	T8786	T8785	punct	=,7
R5909	T8787	T8788	punct	(,TTD
R591	T931	T930	amod	other,hand
R5910	T8788	T8785	parataxis	TTD,7
R5911	T8789	T8788	compound	XpdTTD,TTD
R5912	T8790	T8788	punct	/,TTD
R5913	T8791	T8788	punct	),TTD
R5914	T8792	T8780	punct	", ",included
R5915	T8793	T8794	nsubj	n,2
R5916	T8794	T8780	ccomp	2,included
R5917	T8795	T8794	punct	=,2
R5918	T8796	T8797	punct	(,KO
R5919	T8797	T8794	parataxis	KO,2
R592	T932	T924	punct	", ",are
R5920	T8798	T8797	compound	XpdTTD,KO
R5921	T8799	T8797	punct	/,KO
R5922	T8800	T8797	punct	),KO
R5923	T8801	T8780	punct	", ",included
R5924	T8802	T8803	nsubj	n,4
R5925	T8803	T8780	ccomp	4,included
R5926	T8804	T8803	punct	=,4
R5927	T8805	T8806	punct	(,†XPCS
R5928	T8806	T8803	parataxis	†XPCS,4
R5929	T8807	T8806	compound	XpdTTD,†XPCS
R593	T933	T934	amod	segmental,disorders
R5930	T8808	T8806	punct	/,†XPCS
R5931	T8809	T8806	punct	),†XPCS
R5932	T8810	T8780	punct	", ",included
R5933	T8811	T8812	nsubj	n,2
R5934	T8812	T8780	ccomp	2,included
R5935	T8813	T8812	punct	=,2
R5936	T8814	T8815	punct	(,†XP
R5937	T8815	T8812	parataxis	†XP,2
R5938	T8816	T8815	compound	XpdTTD,†XP
R5939	T8817	T8815	punct	/,†XP
R594	T934	T924	attr	disorders,are
R5940	T8818	T8815	punct	),†XP
R5941	T8819	T8780	punct	;,included
R5942	T8820	T8821	quantmod	1,2
R5943	T8821	T8823	nummod	2,lines
R5944	T8822	T8821	punct	–,2
R5945	T8823	T8780	nsubjpass	lines,included
R5946	T8824	T8823	compound	cell,lines
R5947	T8825	T8823	prep	per,lines
R5948	T8826	T8825	pobj	genotype,per
R5949	T8827	T8780	auxpass	were,included
R595	T935	T934	amod	progeroid,disorders
R5950	T8828	T8780	prep	in,included
R5951	T8829	T8830	det	each,experiment
R5952	T8830	T8828	pobj	experiment,in
R5953	T8831	T8780	punct	.,included
R5954	T8833	T8834	punct	(,D
R5955	T8834	T8835	meta	D,activity
R5956	T8836	T8834	punct	),D
R5957	T8837	T8838	compound	Incision,excision
R5958	T8838	T8835	compound	excision,activity
R5959	T8839	T8838	punct	/,excision
R596	T936	T934	acl	characterised,disorders
R5960	T8840	T8835	prep	of,activity
R5961	T8841	T8840	pobj	combinations,of
R5962	T8842	T8841	prep	of,combinations
R5963	T8843	T8844	amod	altered,complexes
R5964	T8844	T8842	pobj	complexes,of
R5965	T8845	T8844	compound	TFIIH,complexes
R5966	T8846	T8844	prep	in,complexes
R5967	T8847	T8848	det	a,reaction
R5968	T8848	T8846	pobj	reaction,in
R5969	T8849	T8848	amod	reconstituted,reaction
R597	T937	T936	agent	by,characterised
R5970	T8850	T8848	compound	NER,reaction
R5971	T8851	T8835	punct	.,activity
R5972	T8853	T8854	amod	Equal,amounts
R5973	T8854	T8855	nsubjpass	amounts,mixed
R5974	T8856	T8854	prep	of,amounts
R5975	T8857	T8858	amod	single,populations
R5976	T8858	T8856	pobj	populations,of
R5977	T8859	T8857	cc	or,single
R5978	T8860	T8857	conj	mixed,single
R5979	T8861	T8858	prep	of,populations
R598	T938	T939	amod	progressive,failure
R5980	T8862	T8863	amod	recombinant,TFIIHs
R5981	T8863	T8861	pobj	TFIIHs,of
R5982	T8864	T8858	punct	(,populations
R5983	T8865	T8858	acl	containing,populations
R5984	T8866	T8865	dobj	XPD,containing
R5985	T8867	T8866	punct	", ",XPD
R5986	T8868	T8866	conj	XPB,XPD
R5987	T8869	T8868	punct	", ",XPB
R5988	T8870	T8868	conj	p62,XPB
R5989	T8871	T8870	punct	", ",p62
R599	T939	T937	pobj	failure,by
R5990	T8872	T8870	conj	p52,p62
R5991	T8873	T8872	punct	", ",p52
R5992	T8874	T8875	compound	His,p44
R5993	T8875	T8872	conj	p44,p52
R5994	T8876	T8875	punct	-,p44
R5995	T8877	T8875	punct	", ",p44
R5996	T8878	T8879	compound	Flag,p34
R5997	T8879	T8875	conj	p34,p44
R5998	T8880	T8879	punct	-,p34
R5999	T8881	T8879	punct	", ",p34
R6	T91	T92	amod	Homozygous,Alleles
R60	T149	T148	prep	in,differences
R600	T940	T939	amod	post-natal,failure
R6000	T8882	T8879	conj	cdk7,p34
R6001	T8883	T8882	punct	", ",cdk7
R6002	T8884	T8885	compound	cyclin,H
R6003	T8885	T8882	conj	H,cdk7
R6004	T8886	T8885	punct	", ",H
R6005	T8887	T8885	conj	Mat1,H
R6006	T8888	T8887	punct	", ",Mat1
R6007	T8889	T8887	cc	and,Mat1
R6008	T8890	T8887	conj	p8,Mat1
R6009	T8891	T8855	punct	),mixed
R601	T941	T939	compound	growth,failure
R6010	T8892	T8855	auxpass	were,mixed
R6011	T8893	T8855	prep	with,mixed
R6012	T8894	T8895	amod	recombinant,XPG
R6013	T8895	T8893	pobj	XPG,with
R6014	T8896	T8895	punct	", ",XPG
R6015	T8897	T8898	compound	XPF,ERCC1
R6016	T8898	T8895	appos	ERCC1,XPG
R6017	T8899	T8898	punct	/,ERCC1
R6018	T8900	T8895	punct	", ",XPG
R6019	T8901	T8902	compound	XPC,hHR23B
R602	T942	T939	cc	and,failure
R6020	T8902	T8895	appos	hHR23B,XPG
R6021	T8903	T8902	punct	/,hHR23B
R6022	T8904	T8895	punct	", ",XPG
R6023	T8905	T8895	appos	RPA,XPG
R6024	T8906	T8895	punct	", ",XPG
R6025	T8907	T8895	cc	and,XPG
R6026	T8908	T8909	det	a,substrate
R6027	T8909	T8895	conj	substrate,XPG
R6028	T8910	T8909	amod	radiolabelled,substrate
R6029	T8911	T8909	amod	synthetic,substrate
R603	T943	T944	amod	primary,demyelination
R6030	T8912	T8909	compound	NER,substrate
R6031	T8913	T8855	punct	.,mixed
R6032	T8915	T8916	det	The,products
R6033	T8916	T8918	nsubjpass	products,visualised
R6034	T8917	T8916	compound	excision,products
R6035	T8919	T8920	punct	(,nucleotides
R6036	T8920	T8916	parataxis	nucleotides,products
R6037	T8921	T8922	quantmod	26,34
R6038	T8922	T8920	nummod	34,nucleotides
R6039	T8923	T8922	punct	–,34
R604	T944	T939	conj	demyelination,failure
R6040	T8924	T8920	prep	in,nucleotides
R6041	T8925	T8924	pobj	length,in
R6042	T8926	T8920	punct	),nucleotides
R6043	T8927	T8918	auxpass	were,visualised
R6044	T8928	T8918	prep	at,visualised
R6045	T8929	T8930	compound	nucleotide,resolution
R6046	T8930	T8928	pobj	resolution,at
R6047	T8931	T8918	prep	on,visualised
R6048	T8932	T8933	det	a,gel
R6049	T8933	T8931	pobj	gel,on
R605	T945	T944	acl	resulting,demyelination
R6050	T8934	T8933	amod	denaturing,gel
R6051	T8935	T8933	compound	polyacrylamide,gel
R6052	T8936	T8937	mark	as,indicated
R6053	T8937	T8918	advcl	indicated,visualised
R6054	T8938	T8918	punct	.,visualised
R6055	T8941	T8942	det	the,activity
R6056	T8942	T8940	dobj	activity,Note
R6057	T8943	T8942	amod	weak,activity
R6058	T8944	T8942	acl	corresponding,activity
R6059	T8945	T8944	prep	to,corresponding
R606	T946	T945	prep	in,resulting
R6060	T8946	T8947	det	each,complex
R6061	T8947	T8945	pobj	complex,to
R6062	T8948	T8947	amod	single,complex
R6063	T8949	T8948	cc	and,single
R6064	T8950	T8948	conj	combined,single
R6065	T8951	T8947	compound	TFIIH,complex
R6066	T8952	T8953	punct	(,3
R6067	T8953	T8947	parataxis	3,complex
R6068	T8954	T8953	nmod	lanes,3
R6069	T8955	T8956	punct	–,8
R607	T947	T948	amod	severe,neurodysfunction
R6070	T8956	T8953	prep	8,3
R6071	T8957	T8953	punct	),3
R6072	T8958	T8944	advcl	relative,corresponding
R6073	T8959	T8958	prep	to,relative
R6074	T8960	T8961	det	the,wt
R6075	T8961	T8959	pobj	wt,to
R6076	T8962	T8963	punct	(,lane
R6077	T8963	T8961	parataxis	lane,wt
R6078	T8964	T8963	nummod	1,lane
R6079	T8965	T8963	punct	),lane
R608	T948	T946	pobj	neurodysfunction,in
R6080	T8966	T8961	cc	and,wt
R6081	T8967	T8968	amod	negative,controls
R6082	T8968	T8961	conj	controls,wt
R6083	T8969	T8970	punct	(,lane
R6084	T8970	T8968	parataxis	lane,controls
R6085	T8971	T8970	nummod	2,lane
R6086	T8972	T8970	punct	),lane
R6087	T8973	T8940	punct	.,Note
R6088	T8975	T8976	punct	(,E
R6089	T8976	T8977	meta	E,reduction
R609	T949	T924	punct	", ",are
R6090	T8978	T8976	punct	),E
R6091	T8979	T8977	nmod	Xpd,reduction
R6092	T8980	T8981	npadvmod	dose,dependent
R6093	T8981	T8977	amod	dependent,reduction
R6094	T8982	T8981	punct	-,dependent
R6095	T8983	T8977	prep	of,reduction
R6096	T8984	T8983	pobj	TFIIH,of
R6097	T8985	T8977	prep	in,reduction
R6098	T8986	T8987	amod	homozygous,TTD
R6099	T8987	T8990	nmod	TTD,cells
R61	T150	T149	pobj	environment,in
R610	T950	T951	cc	but,without
R6100	T8988	T8987	nmod	XpdTTD,TTD
R6101	T8989	T8987	punct	/,TTD
R6102	T8990	T8985	pobj	cells,in
R6103	T8991	T8987	punct	", ",TTD
R6104	T8992	T8993	amod	hemizygous,KO
R6105	T8993	T8987	conj	KO,TTD
R6106	T8994	T8993	compound	XpdTTD,KO
R6107	T8995	T8993	punct	/,KO
R6108	T8996	T8993	punct	", ",KO
R6109	T8997	T8993	cc	and,KO
R611	T951	T924	prep	without,are
R6110	T8998	T8999	nmod	compound,†XPCS
R6111	T8999	T8993	conj	†XPCS,KO
R6112	T9000	T8999	amod	heterozygous,†XPCS
R6113	T9001	T8999	compound	XpdTTD,†XPCS
R6114	T9002	T8999	punct	/,†XPCS
R6115	T9003	T8999	cc	and,†XPCS
R6116	T9004	T9005	compound	XpdTTD,†XP
R6117	T9005	T8999	conj	†XP,†XPCS
R6118	T9006	T9005	punct	/,†XP
R6119	T9007	T8977	prep	by,reduction
R612	T952	T953	det	a,predisposition
R6120	T9008	T9009	amod	comparative,immunofluorescence
R6121	T9009	T9007	pobj	immunofluorescence,by
R6122	T9010	T9009	prep	of,immunofluorescence
R6123	T9011	T9012	det	the,subunit
R6124	T9012	T9010	pobj	subunit,of
R6125	T9013	T9012	compound	p62,subunit
R6126	T9014	T9012	prep	of,subunit
R6127	T9015	T9014	pobj	TFIIH,of
R6128	T9016	T8977	punct	.,reduction
R6129	T9018	T9019	amod	Roman,numerals
R613	T953	T951	pobj	predisposition,without
R6130	T9019	T9020	nsubj	numerals,represent
R6131	T9021	T9022	amod	different,slides
R6132	T9022	T9020	dobj	slides,represent
R6133	T9023	T9022	amod	microscopic,slides
R6134	T9024	T9020	cc	and,represent
R6135	T9025	T9026	amod	Arabic,numerals
R6136	T9026	T9027	nsubj	numerals,lines
R6137	T9027	T9020	conj	lines,represent
R6138	T9028	T9027	amod	different,lines
R6139	T9029	T9027	compound	cell,lines
R614	T954	T953	amod	clear,predisposition
R6140	T9030	T9027	acl	labelled,lines
R6141	T9031	T9032	mark	as,follows
R6142	T9032	T9030	advcl	follows,labelled
R6143	T9033	T9027	punct	: ,lines
R6144	T9034	T9035	punct	(,I
R6145	T9035	T9036	meta	I,cells
R6146	T9036	T9027	dep	cells,lines
R6147	T9037	T9035	punct	),I
R6148	T9038	T9036	compound	wt,cells
R6149	T9039	T9040	punct	(,1
R615	T955	T953	compound	cancer,predisposition
R6150	T9040	T9036	parataxis	1,cells
R6151	T9041	T9040	punct	),1
R6152	T9042	T9036	acl	labelled,cells
R6153	T9043	T9042	prep	with,labelled
R6154	T9044	T9045	nummod	2,μm
R6155	T9045	T9047	compound	μm,beads
R6156	T9046	T9045	punct	-,μm
R6157	T9047	T9043	pobj	beads,with
R6158	T9048	T9036	punct	", ",cells
R6159	T9049	T9050	compound	XpdTTD,TTD
R616	T956	T957	punct	[,12
R6160	T9050	T9052	compound	TTD,cells
R6161	T9051	T9050	punct	/,TTD
R6162	T9052	T9036	conj	cells,cells
R6163	T9053	T9054	punct	(,2
R6164	T9054	T9052	parataxis	2,cells
R6165	T9055	T9054	punct	),2
R6166	T9056	T9052	prep	with,cells
R6167	T9057	T9058	nummod	0.79,μm
R6168	T9058	T9060	compound	μm,beads
R6169	T9059	T9058	punct	-,μm
R617	T957	T924	parataxis	12,are
R6170	T9060	T9056	pobj	beads,with
R6171	T9061	T9052	punct	", ",cells
R6172	T9062	T9052	cc	and,cells
R6173	T9063	T9064	compound	XpdTTD,KO
R6174	T9064	T9066	compound	KO,cells
R6175	T9065	T9064	punct	/,KO
R6176	T9066	T9052	conj	cells,cells
R6177	T9067	T9068	punct	(,3
R6178	T9068	T9066	parataxis	3,cells
R6179	T9069	T9068	punct	),3
R618	T958	T959	punct	–,15
R6180	T9070	T9066	prep	with,cells
R6181	T9071	T9072	det	no,beads
R6182	T9072	T9070	pobj	beads,with
R6183	T9073	T9036	punct	;,cells
R6184	T9074	T9075	punct	(,II
R6185	T9075	T9076	meta	II,cells
R6186	T9076	T9036	conj	cells,cells
R6187	T9077	T9075	punct	),II
R6188	T9078	T9076	compound	wt,cells
R6189	T9079	T9080	punct	(,1
R619	T959	T957	prep	15,12
R6190	T9080	T9076	parataxis	1,cells
R6191	T9081	T9080	punct	),1
R6192	T9082	T9076	acl	labelled,cells
R6193	T9083	T9082	prep	with,labelled
R6194	T9084	T9085	nummod	0.79,μm
R6195	T9085	T9087	compound	μm,beads
R6196	T9086	T9085	punct	-,μm
R6197	T9087	T9083	pobj	beads,with
R6198	T9088	T9076	cc	and,cells
R6199	T9089	T9090	compound	XpdTTD,†XPCS
R62	T151	T150	cc	or,environment
R620	T960	T957	punct	],12
R6200	T9090	T9092	compound	†XPCS,cells
R6201	T9091	T9090	punct	/,†XPCS
R6202	T9092	T9076	conj	cells,cells
R6203	T9093	T9094	punct	(,4
R6204	T9094	T9092	parataxis	4,cells
R6205	T9095	T9094	punct	),4
R6206	T9096	T9092	prep	with,cells
R6207	T9097	T9098	det	no,beads
R6208	T9098	T9096	pobj	beads,with
R6209	T9099	T9076	punct	;,cells
R621	T961	T924	punct	.,are
R6210	T9100	T9076	cc	and,cells
R6211	T9101	T9102	punct	(,III
R6212	T9102	T9103	meta	III,cells
R6213	T9103	T9076	conj	cells,cells
R6214	T9104	T9102	punct	),III
R6215	T9105	T9103	compound	wt,cells
R6216	T9106	T9107	punct	(,1
R6217	T9107	T9103	parataxis	1,cells
R6218	T9108	T9107	punct	),1
R6219	T9109	T9103	acl	labelled,cells
R622	T963	T964	nsubj	Patients,display
R6220	T9110	T9109	prep	with,labelled
R6221	T9111	T9112	nummod	0.79,μm
R6222	T9112	T9114	compound	μm,beads
R6223	T9113	T9112	punct	-,μm
R6224	T9114	T9110	pobj	beads,with
R6225	T9115	T9103	cc	and,cells
R6226	T9116	T9117	compound	XpdTTD,†XP
R6227	T9117	T9119	compound	†XP,cells
R6228	T9118	T9117	punct	/,†XP
R6229	T9119	T9103	conj	cells,cells
R623	T965	T963	prep	with,Patients
R6230	T9120	T9121	punct	(,5
R6231	T9121	T9119	parataxis	5,cells
R6232	T9122	T9121	punct	),5
R6233	T9123	T9119	prep	with,cells
R6234	T9124	T9125	det	no,beads
R6235	T9125	T9123	pobj	beads,with
R6236	T9126	T9027	punct	.,lines
R6237	T9128	T9129	punct	(,F
R6238	T9129	T9130	meta	F,Quantification
R6239	T9131	T9129	punct	),F
R624	T966	T965	pobj	TTD,with
R6240	T9132	T9130	prep	of,Quantification
R6241	T9133	T9134	amod	immunofluorescent,signal
R6242	T9134	T9132	pobj	signal,of
R6243	T9135	T9134	prep	from,signal
R6244	T9136	T9137	advmod	at,50
R6245	T9137	T9139	nummod	50,nuclei
R6246	T9138	T9137	advmod	least,50
R6247	T9139	T9135	pobj	nuclei,from
R6248	T9140	T9139	prep	per,nuclei
R6249	T9141	T9142	compound	cell,line
R625	T967	T964	advmod	additionally,display
R6250	T9142	T9140	pobj	line,per
R6251	T9143	T9139	cc	and,nuclei
R6252	T9144	T9145	quantmod	2,6
R6253	T9145	T9147	nummod	6,experiments
R6254	T9146	T9145	punct	–,6
R6255	T9147	T9139	conj	experiments,nuclei
R6256	T9148	T9147	prep	per,experiments
R6257	T9149	T9148	pobj	genotype,per
R6258	T9150	T9130	punct	.,Quantification
R6259	T9152	T9153	nsubjpass	Bars,depicted
R626	T968	T969	nmod	hallmark,hair
R6260	T9154	T9152	acl	representing,Bars
R6261	T9155	T9154	dobj	cells,representing
R6262	T9156	T9155	acl	analysed,cells
R6263	T9157	T9156	prep	on,analysed
R6264	T9158	T9159	det	the,slide
R6265	T9159	T9157	pobj	slide,on
R6266	T9160	T9159	amod	same,slide
R6267	T9161	T9159	amod	microscopic,slide
R6268	T9162	T9153	auxpass	are,depicted
R6269	T9163	T9153	npadvmod	side,depicted
R627	T969	T964	dobj	hair,display
R6270	T9164	T9163	prep	by,side
R6271	T9165	T9164	pobj	side,by
R6272	T9166	T9153	punct	", ",depicted
R6273	T9167	T9153	prep	with,depicted
R6274	T9168	T9167	pobj	wt,with
R6275	T9169	T9168	acl	set,wt
R6276	T9170	T9169	prep	at,set
R6277	T9171	T9172	nummod	100,%
R6278	T9172	T9170	pobj	%,at
R6279	T9173	T9153	punct	.,depicted
R628	T970	T971	npadvmod	sulphur,deficient
R6280	T9175	T9176	det	The,value
R6281	T9176	T9179	nsubj	value,indicates
R6282	T9177	T9176	compound	p,value
R6283	T9178	T9176	punct	-,value
R6284	T9180	T9181	amod	minimum,difference
R6285	T9181	T9179	dobj	difference,indicates
R6286	T9182	T9181	amod	significant,difference
R6287	T9183	T9181	prep	between,difference
R6288	T9184	T9183	pobj	wt,between
R6289	T9185	T9184	cc	and,wt
R629	T971	T969	amod	deficient,hair
R6290	T9186	T9187	det	the,lines
R6291	T9187	T9184	conj	lines,wt
R6292	T9188	T9187	amod	indicated,lines
R6293	T9189	T9187	compound	cell,lines
R6294	T9190	T9187	acl	analysed,lines
R6295	T9191	T9190	prep	on,analysed
R6296	T9192	T9193	det	the,slide
R6297	T9193	T9191	pobj	slide,on
R6298	T9194	T9193	amod	same,slide
R6299	T9195	T9193	amod	microscopic,slide
R63	T152	T153	amod	genetic,background
R630	T972	T971	punct	-,deficient
R6300	T9196	T9181	prep	within,difference
R6301	T9197	T9198	nummod	one,experiment
R6302	T9198	T9196	pobj	experiment,within
R6303	T9199	T9179	punct	.,indicates
R6304	T9212	T9211	prep	of,Frequency
R6305	T9213	T9214	compound	Xpd†XP,†XP
R6306	T9214	T9212	pobj	†XP,of
R6307	T9215	T9214	punct	/,†XP
R6308	T9216	T9214	punct	", ",†XP
R6309	T9217	T9218	compound	Xpd†XPCS,†XPCS
R631	T973	T969	amod	brittle,hair
R6310	T9218	T9214	conj	†XPCS,†XP
R6311	T9219	T9218	punct	/,†XPCS
R6312	T9220	T9218	punct	", ",†XPCS
R6313	T9221	T9218	cc	and,†XPCS
R6314	T9222	T9223	nmod	Compound,†XPCS
R6315	T9223	T9218	conj	†XPCS,†XPCS
R6316	T9224	T9223	amod	Heterozygous,†XPCS
R6317	T9225	T9223	compound	Xpd†XP,†XPCS
R6318	T9226	T9223	punct	/,†XPCS
R6319	T9227	T9214	appos	Embryos,†XP
R632	T974	T969	cc	and,hair
R6320	T9228	T9227	cc	and,Embryos
R6321	T9229	T9227	conj	Offspring,Embryos
R6322	T9241	T9242	amod	Pleiotropic,Effects
R6323	T9243	T9242	nmod	Xpd,Effects
R6324	T9244	T9242	amod	Biallelic,Effects
R6325	T9245	T9242	prep	in,Effects
R6326	T9246	T9245	pobj	Mice,in
R6327	T9247	T9246	cc	and,Mice
R6328	T9248	T9246	conj	Cells,Mice
R6329	T9280	T9281	compound	Genotype,Phenotype
R633	T975	T969	conj	nails,hair
R6330	T9281	T9283	compound	Phenotype,Relationships
R6331	T9282	T9281	punct	–,Phenotype
R6332	T9284	T9283	prep	in,Relationships
R6333	T9285	T9286	compound	XPD,Disorders
R6334	T9286	T9284	pobj	Disorders,in
R6335	T9288	T9289	prep	According,determined
R6336	T9290	T9288	prep	to,According
R6337	T9291	T9292	det	the,hypothesis
R6338	T9292	T9290	pobj	hypothesis,to
R6339	T9293	T9292	amod	current,hypothesis
R634	T976	T969	cc	and,hair
R6340	T9294	T9292	amod	monoallelic,hypothesis
R6341	T9295	T9289	punct	", ",determined
R6342	T9296	T9289	nsubjpass	phenotype,determined
R6343	T9297	T9289	auxpass	is,determined
R6344	T9298	T9299	advmod	solely,by
R6345	T9299	T9289	agent	by,determined
R6346	T9300	T9301	det	the,product
R6347	T9301	T9299	pobj	product,by
R6348	T9302	T9301	amod	causative,product
R6349	T9303	T9301	compound	allele,product
R635	T977	T978	amod	scaling,skin
R6350	T9304	T9289	punct	.,determined
R6351	T9306	T9307	mark	If,is
R6352	T9307	T9313	advcl	is,considered
R6353	T9308	T9309	det	a,allele
R6354	T9309	T9307	nsubj	allele,is
R6355	T9310	T9309	amod	second,allele
R6356	T9311	T9309	punct	", ",allele
R6357	T9312	T9309	amod	different,allele
R6358	T9314	T9307	acomp	present,is
R6359	T9315	T9313	punct	", ",considered
R636	T978	T969	conj	skin,hair
R6360	T9316	T9313	nsubjpass	it,considered
R6361	T9317	T9313	auxpass	is,considered
R6362	T9318	T9319	det	a,null
R6363	T9319	T9313	oprd	null,considered
R6364	T9320	T9319	amod	functional,null
R6365	T9321	T9313	punct	.,considered
R6366	T9323	T9324	expl	There,is
R6367	T9325	T9326	det	a,lack
R6368	T9326	T9324	attr	lack,is
R6369	T9327	T9326	prep	of,lack
R637	T979	T980	punct	[,13
R6370	T9328	T9329	det	any,correlation
R6371	T9329	T9327	pobj	correlation,of
R6372	T9330	T9329	prep	between,correlation
R6373	T9331	T9332	det	the,site
R6374	T9332	T9330	pobj	site,between
R6375	T9333	T9332	prep	of,site
R6376	T9334	T9335	det	the,mutation
R6377	T9335	T9333	pobj	mutation,of
R6378	T9336	T9335	compound	XPD,mutation
R6379	T9337	T9332	cc	and,site
R638	T980	T969	parataxis	13,hair
R6380	T9338	T9339	det	the,disorder
R6381	T9339	T9332	conj	disorder,site
R6382	T9340	T9339	amod	resulting,disorder
R6383	T9341	T9324	punct	.,is
R6384	T9343	T9344	nsubj	We,propose
R6385	T9345	T9346	det	a,hypothesis
R6386	T9346	T9344	dobj	hypothesis,propose
R6387	T9347	T9346	amod	biallelic,hypothesis
R6388	T9348	T9346	prep	for,hypothesis
R6389	T9349	T9350	compound	compound,heterozygotes
R639	T981	T980	punct	],13
R6390	T9350	T9348	pobj	heterozygotes,for
R6391	T9351	T9352	prep	in,contribute
R6392	T9352	T9346	relcl	contribute,hypothesis
R6393	T9353	T9351	pobj	which,in
R6394	T9354	T9355	det	both,alleles
R6395	T9355	T9352	nsubj	alleles,contribute
R6396	T9356	T9352	aux	can,contribute
R6397	T9357	T9352	prep	to,contribute
R6398	T9358	T9359	det	the,phenotype
R6399	T9359	T9357	pobj	phenotype,to
R64	T153	T150	conj	background,environment
R640	T982	T969	punct	", ",hair
R6400	T9360	T9344	punct	.,propose
R6401	T9362	T9363	nsubjpass	Examples,provided
R6402	T9364	T9362	prep	of,Examples
R6403	T9365	T9366	nmod	compound,patients
R6404	T9366	T9364	pobj	patients,of
R6405	T9367	T9366	amod	heterozygous,patients
R6406	T9368	T9369	prep	in,is
R6407	T9369	T9366	relcl	is,patients
R6408	T9370	T9368	pobj	which,in
R6409	T9371	T9372	det	a,allele
R641	T983	T969	acl	resulting,hair
R6410	T9372	T9369	nsubj	allele,is
R6411	T9373	T9372	amod	second,allele
R6412	T9374	T9372	punct	", ",allele
R6413	T9375	T9376	amod	presumed,null
R6414	T9376	T9372	amod	null,allele
R6415	T9377	T9369	acomp	likely,is
R6416	T9378	T9379	aux	to,contribute
R6417	T9379	T9377	xcomp	contribute,likely
R6418	T9380	T9379	prep	to,contribute
R6419	T9381	T9382	compound	disease,outcome
R642	T984	T983	prep	from,resulting
R6420	T9382	T9380	pobj	outcome,to
R6421	T9383	T9363	auxpass	are,provided
R6422	T9384	T9363	advmod	above,provided
R6423	T9385	T9363	prep	in,provided
R6424	T9386	T9385	pobj	comparison,in
R6425	T9387	T9386	prep	to,comparison
R6426	T9388	T9389	amod	corresponding,patients
R6427	T9389	T9387	pobj	patients,to
R6428	T9390	T9391	advmod	homo,hemizygous
R6429	T9391	T9389	amod	hemizygous,patients
R643	T985	T986	det	a,defect
R6430	T9392	T9391	punct	-,hemizygous
R6431	T9393	T9391	cc	or,hemizygous
R6432	T9394	T9389	prep	with,patients
R6433	T9395	T9396	det	the,allele
R6434	T9396	T9394	pobj	allele,with
R6435	T9397	T9396	amod	same,allele
R6436	T9398	T9396	amod	causative,allele
R6437	T9399	T9363	punct	.,provided
R6438	T9401	T9402	nsubj	Numbers,indicate
R6439	T9403	T9401	prep	in,Numbers
R644	T986	T984	pobj	defect,from
R6440	T9404	T9405	det	the,schematic
R6441	T9405	T9403	pobj	schematic,in
R6442	T9406	T9405	prep	of,schematic
R6443	T9407	T9408	det	the,protein
R6444	T9408	T9406	pobj	protein,of
R6445	T9409	T9410	det	the,domains
R6446	T9410	T9402	dobj	domains,indicate
R6447	T9411	T9410	compound	helicase,domains
R6448	T9412	T9402	punct	.,indicate
R645	T987	T986	amod	basal,defect
R646	T988	T986	compound	transcription,defect
R647	T989	T986	prep	in,defect
R648	T990	T991	amod	specific,types
R649	T991	T989	pobj	types,in
R65	T154	T134	punct	.,is
R650	T992	T991	compound	cell,types
R651	T993	T994	punct	[,17
R652	T994	T964	parataxis	17,display
R653	T995	T994	nummod	16,17
R654	T996	T994	punct	",",17
R655	T997	T994	punct	],17
R656	T998	T964	punct	.,display
R657	T1000	T1001	det	A,disorder
R658	T1001	T1003	nsubjpass	disorder,described
R659	T1002	T1001	amod	related,disorder
R66	T156	T157	nsubj	We,addressed
R660	T1004	T1001	prep	with,disorder
R661	T1005	T1006	det	the,predisposition
R662	T1006	T1004	pobj	predisposition,with
R663	T1007	T1006	compound	cancer,predisposition
R664	T1008	T1006	prep	of,predisposition
R665	T1009	T1008	pobj	XP,of
R666	T1010	T1006	acl	combined,predisposition
R667	T1011	T1010	prep	with,combined
R668	T1012	T1013	det	the,complications
R669	T1013	T1011	pobj	complications,with
R67	T158	T159	det	the,potential
R670	T1014	T1013	amod	neurodevelopmental,complications
R671	T1015	T1013	prep	of,complications
R672	T1016	T1015	pobj	CS,of
R673	T1017	T1018	punct	(,XPCS
R674	T1018	T1016	parataxis	XPCS,CS
R675	T1019	T1018	punct	),XPCS
R676	T1020	T1003	punct	", ",described
R677	T1021	T1022	mark	although,rare
R678	T1022	T1003	advcl	rare,described
R679	T1023	T1003	punct	", ",described
R68	T159	T157	dobj	potential,addressed
R680	T1024	T1003	aux	has,described
R681	T1025	T1003	advmod	also,described
R682	T1026	T1003	auxpass	been,described
R683	T1027	T1028	punct	[,18
R684	T1028	T1003	parataxis	18,described
R685	T1029	T1028	punct	],18
R686	T1030	T1003	punct	.,described
R687	T1032	T1033	amod	Many,mutations
R688	T1033	T1035	nsubjpass	mutations,associated
R689	T1034	T1033	compound	XPD,mutations
R69	T160	T159	prep	of,potential
R690	T1036	T1035	auxpass	are,associated
R691	T1037	T1035	prep	with,associated
R692	T1038	T1039	det	an,phenotype
R693	T1039	T1037	pobj	phenotype,with
R694	T1040	T1039	amod	exclusive,phenotype
R695	T1041	T1039	compound	disease,phenotype
R696	T1042	T1043	punct	(,XPDR722W
R697	T1043	T1039	parataxis	XPDR722W,phenotype
R698	T1044	T1043	advmod	e.g.,XPDR722W
R699	T1045	T1043	punct	", ",XPDR722W
R7	T92	T90	pobj	Alleles,by
R70	T161	T162	amod	different,alleles
R700	T1046	T1043	prep	with,XPDR722W
R701	T1047	T1046	pobj	TTD,with
R702	T1048	T1043	cc	and,XPDR722W
R703	T1049	T1043	conj	XPDR683W,XPDR722W
R704	T1050	T1049	prep	with,XPDR683W
R705	T1051	T1050	pobj	XP,with
R706	T1052	T1043	punct	),XPDR722W
R707	T1053	T1035	cc	and,associated
R708	T1054	T1055	auxpass	are,viewed
R709	T1055	T1035	conj	viewed,associated
R71	T162	T160	pobj	alleles,of
R710	T1056	T1055	advmod	thus,viewed
R711	T1057	T1055	prep	as,viewed
R712	T1058	T1057	pobj	causative,as
R713	T1059	T1058	prep	of,causative
R714	T1060	T1061	det	the,syndromes
R715	T1061	T1059	pobj	syndromes,of
R716	T1062	T1061	amod	corresponding,syndromes
R717	T1063	T1035	punct	.,associated
R718	T1065	T1066	nsubjpass	Alleles,considered
R719	T1067	T1068	neg	not,associated
R72	T163	T162	amod	recessive,alleles
R720	T1068	T1065	acl	associated,Alleles
R721	T1069	T1068	advmod	exclusively,associated
R722	T1070	T1068	prep	with,associated
R723	T1071	T1072	nummod	one,disorder
R724	T1072	T1070	pobj	disorder,with
R725	T1073	T1066	auxpass	are,considered
R726	T1074	T1075	punct	“,alleles
R727	T1075	T1066	oprd	alleles,considered
R728	T1076	T1077	advmod	likely,null
R729	T1077	T1075	amod	null,alleles
R73	T164	T165	aux	to,contribute
R730	T1078	T1075	punct	”,alleles
R731	T1079	T1080	punct	[,20
R732	T1080	T1066	parataxis	20,considered
R733	T1081	T1080	nummod	19,20
R734	T1082	T1080	punct	",",20
R735	T1083	T1080	punct	],20
R736	T1084	T1066	punct	.,considered
R737	T1086	T1087	nsubj	Some,fail
R738	T1088	T1086	prep	of,Some
R739	T1089	T1090	det	these,alleles
R74	T165	T159	acl	contribute,potential
R740	T1090	T1088	pobj	alleles,of
R741	T1091	T1092	aux	to,support
R742	T1092	T1087	xcomp	support,fail
R743	T1093	T1092	dobj	viability,support
R744	T1094	T1092	prep	in,support
R745	T1095	T1096	det	a,strain
R746	T1096	T1094	pobj	strain,in
R747	T1097	T1096	amod	haploid,strain
R748	T1098	T1096	compound	Schizosaccharomyces,strain
R749	T1099	T1096	compound	pombe,strain
R75	T166	T165	prep	to,contribute
R750	T1100	T1096	compound	yeast,strain
R751	T1101	T1096	prep	with,strain
R752	T1102	T1103	det	a,mutation
R753	T1103	T1101	pobj	mutation,with
R754	T1104	T1103	amod	null,mutation
R755	T1105	T1103	prep	in,mutation
R756	T1106	T1107	det	the,rad15
R757	T1107	T1105	pobj	rad15,in
R758	T1108	T1107	compound	XPD,rad15
R759	T1109	T1107	compound	homologue,rad15
R76	T167	T168	det	the,pleiotropy
R760	T1110	T1087	cc	and,fail
R761	T1111	T1112	auxpass	are,considered
R762	T1112	T1087	conj	considered,fail
R763	T1113	T1112	advmod	thus,considered
R764	T1114	T1112	oprd	devoid,considered
R765	T1115	T1114	prep	of,devoid
R766	T1116	T1117	amod	significant,activity
R767	T1117	T1115	pobj	activity,of
R768	T1118	T1117	amod	biological,activity
R769	T1119	T1120	punct	[,19
R77	T168	T166	pobj	pleiotropy,to
R770	T1120	T1112	parataxis	19,considered
R771	T1121	T1120	punct	],19
R772	T1122	T1087	punct	.,fail
R773	T1124	T1125	det	This,classification
R774	T1125	T1126	nsubj	classification,defines
R775	T1127	T1125	prep	of,classification
R776	T1128	T1127	pobj	alleles,of
R777	T1129	T1125	prep	as,classification
R778	T1130	T1131	preconj	either,causative
R779	T1131	T1129	amod	causative,as
R78	T169	T168	amod	enigmatic,pleiotropy
R780	T1132	T1131	cc	or,causative
R781	T1133	T1131	conj	null,causative
R782	T1134	T1126	advmod	currently,defines
R783	T1135	T1136	dep	what,refer
R784	T1136	T1126	ccomp	refer,defines
R785	T1137	T1136	nsubj	we,refer
R786	T1138	T1136	prep	to,refer
R787	T1139	T1136	prep	as,refer
R788	T1140	T1141	det	a,paradigm
R789	T1141	T1139	pobj	paradigm,as
R79	T170	T168	acl	associated,pleiotropy
R790	T1142	T1141	punct	“,paradigm
R791	T1143	T1141	amod	monoallelic,paradigm
R792	T1144	T1141	punct	”,paradigm
R793	T1145	T1141	prep	of,paradigm
R794	T1146	T1147	compound	XPD,disease
R795	T1147	T1145	pobj	disease,of
R796	T1148	T1126	punct	.,defines
R797	T1150	T1151	advmod	However,casts
R798	T1152	T1151	punct	", ",casts
R799	T1153	T1154	det	the,identification
R8	T93	T92	amod	Lethal,Alleles
R80	T171	T170	prep	with,associated
R800	T1154	T1151	nsubj	identification,casts
R801	T1155	T1154	prep	in,identification
R802	T1156	T1157	amod	recent,years
R803	T1157	T1155	pobj	years,in
R804	T1158	T1157	prep	of,years
R805	T1159	T1160	compound	XP,patients
R806	T1160	T1158	pobj	patients,of
R807	T1161	T1160	compound	complementation,patients
R808	T1162	T1163	compound	group,D
R809	T1163	T1160	compound	D,patients
R81	T172	T173	nmod	XPD,disorders
R810	T1164	T1160	prep	with,patients
R811	T1165	T1166	amod	atypical,presentation
R812	T1166	T1164	pobj	presentation,with
R813	T1167	T1166	compound	disease,presentation
R814	T1168	T1166	punct	", ",presentation
R815	T1169	T1166	prep	including,presentation
R816	T1170	T1169	pobj	symptoms,including
R817	T1171	T1170	prep	of,symptoms
R818	T1172	T1173	preconj	both,XP
R819	T1173	T1171	pobj	XP,of
R82	T173	T171	pobj	disorders,with
R820	T1174	T1173	cc	and,XP
R821	T1175	T1173	conj	TTD,XP
R822	T1176	T1177	punct	[,8
R823	T1177	T1154	parataxis	8,identification
R824	T1178	T1177	punct	],8
R825	T1179	T1151	punct	", ",casts
R826	T1180	T1151	dobj	doubt,casts
R827	T1181	T1151	prep	on,casts
R828	T1182	T1183	det	the,ability
R829	T1183	T1181	pobj	ability,on
R83	T174	T173	amod	recessive,disorders
R830	T1184	T1183	prep	of,ability
R831	T1185	T1186	amod	such,paradigm
R832	T1186	T1184	pobj	paradigm,of
R833	T1187	T1186	det	a,paradigm
R834	T1188	T1186	amod	monoallelic,paradigm
R835	T1189	T1190	aux	to,explain
R836	T1190	T1183	acl	explain,ability
R837	T1191	T1192	amod	clinical,heterogeneity
R838	T1192	T1190	dobj	heterogeneity,explain
R839	T1193	T1190	prep	in,explain
R84	T175	T170	prep	in,associated
R840	T1194	T1195	compound	compound,heterozygotes
R841	T1195	T1193	pobj	heterozygotes,in
R842	T1196	T1151	punct	.,casts
R843	T1198	T1199	advmod	Previously,generated
R844	T1200	T1199	punct	", ",generated
R845	T1201	T1199	nsubj	we,generated
R846	T1202	T1203	det	a,model
R847	T1203	T1199	dobj	model,generated
R848	T1204	T1203	compound	TTD,model
R849	T1205	T1203	compound	mouse,model
R85	T176	T177	nmod	compound,models
R850	T1206	T1207	punct	(,XPDR722W
R851	T1207	T1203	parataxis	XPDR722W,model
R852	T1208	T1207	punct	),XPDR722W
R853	T1209	T1210	dep	that,phenocopies
R854	T1210	T1203	relcl	phenocopies,model
R855	T1211	T1212	det	the,syndrome
R856	T1212	T1210	dobj	syndrome,phenocopies
R857	T1213	T1212	amod	human,syndrome
R858	T1214	T1215	punct	[,21
R859	T1215	T1199	parataxis	21,generated
R86	T177	T175	pobj	models,in
R860	T1216	T1215	nummod	15,21
R861	T1217	T1215	punct	",",21
R862	T1218	T1215	punct	],21
R863	T1219	T1199	punct	.,generated
R864	T1221	T1222	advmod	Here,report
R865	T1223	T1222	nsubj	we,report
R866	T1224	T1225	det	the,generation
R867	T1225	T1222	dobj	generation,report
R868	T1226	T1225	prep	of,generation
R869	T1227	T1228	amod	additional,alleles
R87	T178	T177	amod	heterozygous,models
R870	T1228	T1226	pobj	alleles,of
R871	T1229	T1228	amod	mutant,alleles
R872	T1230	T1228	compound	Xpd,alleles
R873	T1231	T1232	dep	that,fail
R874	T1232	T1228	relcl	fail,alleles
R875	T1233	T1234	aux	to,support
R876	T1234	T1232	xcomp	support,fail
R877	T1235	T1234	dobj	viability,support
R878	T1236	T1234	prep	on,support
R879	T1237	T1238	poss	their,own
R88	T179	T177	compound	mouse,models
R880	T1238	T1236	pobj	own,on
R881	T1239	T1232	cc	but,fail
R882	T1240	T1241	advmod	nevertheless,ameliorate
R883	T1241	T1232	conj	ameliorate,fail
R884	T1242	T1243	npadvmod	TTD,associated
R885	T1243	T1245	amod	associated,ageing
R886	T1244	T1243	punct	-,associated
R887	T1245	T1241	dobj	ageing,ameliorate
R888	T1246	T1245	amod	premature,ageing
R889	T1247	T1245	amod	segmental,ageing
R89	T180	T157	punct	.,addressed
R890	T1248	T1245	punct	", ",ageing
R891	T1249	T1250	amod	cutaneous,features
R892	T1250	T1245	conj	features,ageing
R893	T1251	T1250	punct	", ",features
R894	T1252	T1253	amod	cellular,capacity
R895	T1253	T1250	conj	capacity,features
R896	T1254	T1255	compound	DNA,repair
R897	T1255	T1253	compound	repair,capacity
R898	T1256	T1253	punct	", ",capacity
R899	T1257	T1253	cc	and,capacity
R9	T94	T92	compound	Xpd,Alleles
R90	T182	T183	nsubj	Alterations,result
R900	T1258	T1259	compound	UV,survival
R901	T1259	T1253	conj	survival,capacity
R902	T1260	T1261	advmod	when,present
R903	T1261	T1241	advcl	present,ameliorate
R904	T1262	T1261	prep	in,present
R905	T1263	T1264	det	a,state
R906	T1264	T1262	pobj	state,in
R907	T1265	T1264	amod	compound,state
R908	T1266	T1264	compound	heterozygote,state
R909	T1267	T1222	punct	.,report
R91	T184	T182	prep	in,Alterations
R910	T1401	T1400	prep	of,Generation
R911	T1402	T1403	compound	Xpd,Heterozygotes
R912	T1403	T1401	pobj	Heterozygotes,of
R913	T1404	T1403	compound	Compound,Heterozygotes
R914	T1406	T1407	nsubj	We,generated
R915	T1408	T1409	det	an,allele
R916	T1409	T1407	dobj	allele,generated
R917	T1410	T1409	nmod	Xpd,allele
R918	T1411	T1409	amod	knock,allele
R919	T1412	T1411	punct	-,knock
R92	T185	T186	det	this,helicase
R920	T1413	T1411	prt	in,knock
R921	T1414	T1409	prep	with,allele
R922	T1415	T1416	det	a,mutation
R923	T1416	T1414	pobj	mutation,with
R924	T1417	T1416	compound	point,mutation
R925	T1418	T1416	acl	encoding,mutation
R926	T1419	T1420	det	a,change
R927	T1420	T1418	dobj	change,encoding
R928	T1421	T1420	amod	single,change
R929	T1422	T1423	compound	amino,acid
R93	T186	T184	pobj	helicase,in
R930	T1423	T1420	compound	acid,change
R931	T1424	T1425	punct	(,XPDG602D
R932	T1425	T1420	parataxis	XPDG602D,change
R933	T1426	T1425	punct	),XPDG602D
R934	T1427	T1420	acl	found,change
R935	T1428	T1427	prep	in,found
R936	T1429	T1430	det	the,patient
R937	T1430	T1428	pobj	patient,in
R938	T1431	T1430	compound	XPCS,patient
R939	T1432	T1430	appos	XPCS2,patient
R94	T187	T186	amod	essential,helicase
R940	T1433	T1434	punct	(,1A
R941	T1434	T1407	parataxis	1A,generated
R942	T1435	T1434	compound	Figure,1A
R943	T1436	T1437	punct	–,1C
R944	T1437	T1434	prep	1C,1A
R945	T1438	T1434	punct	),1A
R946	T1439	T1407	punct	.,generated
R947	T1441	T1442	compound	mRNA,expression
R948	T1442	T1443	nsubjpass	expression,detected
R949	T1444	T1442	prep	from,expression
R95	T188	T186	punct	", ",helicase
R950	T1445	T1446	det	the,allele
R951	T1446	T1444	pobj	allele,from
R952	T1447	T1446	amod	targeted,allele
R953	T1448	T1443	aux	could,detected
R954	T1449	T1443	auxpass	be,detected
R955	T1450	T1443	prep	in,detected
R956	T1451	T1452	amod	embryonic,cells
R957	T1452	T1450	pobj	cells,in
R958	T1453	T1452	compound	stem,cells
R959	T1454	T1443	prep	by,detected
R96	T189	T186	prep	with,helicase
R960	T1455	T1456	compound	RT,PCR
R961	T1456	T1454	pobj	PCR,by
R962	T1457	T1456	punct	-,PCR
R963	T1458	T1459	punct	(,1D
R964	T1459	T1443	parataxis	1D,detected
R965	T1460	T1459	compound	Figure,1D
R966	T1461	T1459	punct	),1D
R967	T1462	T1443	punct	", ",detected
R968	T1463	T1464	mark	although,reduced
R969	T1464	T1443	advcl	reduced,detected
R97	T190	T189	pobj	functions,with
R970	T1465	T1464	nsubjpass	expression,reduced
R971	T1466	T1464	auxpass	was,reduced
R972	T1467	T1468	advmod	approximately,5
R973	T1468	T1464	npadvmod	5,reduced
R974	T1469	T1468	punct	-,5
R975	T1470	T1468	advmod	fold,5
R976	T1471	T1464	advcl	relative,reduced
R977	T1472	T1471	prep	to,relative
R978	T1473	T1474	compound	wt,levels
R979	T1474	T1472	pobj	levels,to
R98	T191	T190	prep	in,functions
R980	T1475	T1474	compound	mRNA,levels
R981	T1476	T1474	compound	transcript,levels
R982	T1477	T1478	mark	as,determined
R983	T1478	T1464	advcl	determined,reduced
R984	T1479	T1478	prep	by,determined
R985	T1480	T1479	pobj	Northern,by
R986	T1481	T1480	amod	blotting,Northern
R987	T1482	T1480	prep	of,Northern
R988	T1483	T1482	pobj	RNA,of
R989	T1484	T1483	prep	from,RNA
R99	T192	T193	preconj	both,repair
R990	T1485	T1486	det	the,testis
R991	T1486	T1484	pobj	testis,from
R992	T1487	T1486	prep	of,testis
R993	T1488	T1489	amod	heterozygous,animals
R994	T1489	T1487	pobj	animals,of
R995	T1490	T1491	punct	(,1E
R996	T1491	T1443	parataxis	1E,detected
R997	T1492	T1491	compound	Figure,1E
R998	T1493	T1491	punct	),1E
R999	T1494	T1443	punct	.,detected

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PMC:1584416 JSON TXT 8 Projects