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and Methods\n\nDerivation and analysis of mutant mice.\nGeneration of XpdTTD (XPDR722W) and XpdTTD/KO mice has been described previously [21,22]. 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. Chimeric mice and mouse embryonic fibroblasts were generated according to standard procedures. Haematoxylin and eosin staining was performed according to standard procedures. Amino acid analysis was conducted as described in [21]. Blood values were analysed using Animal Blood Counter Vet (ABX Diagnostix, Montpellier, France). Radiographs were taken, and relative bone mineral density was calculated as described in [15]. Mice used in this study were in a 129Ola/C57BL6 mixed background unless noted differently. 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.\n\nUV sensitivity, UV-UDS, UV-RRS, and TFIIH incision/excision activity.\nUV survival, UV-UDS, and UV-RRS assays were performed as described previously [21,30]. 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. 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. For the incision/excision activity assay, recombinant TFIIH was prepared and assayed as described previously [27].\n\nComparative immunofluorescence.\nLatex 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. 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."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T6321","span":{"begin":360,"end":365},"obj":"NCBITaxon:10088"},{"id":"T6322","span":{"begin":366,"end":375},"obj":"UBERON:0000922"},{"id":"T6323","span":{"begin":376,"end":387},"obj":"CL:0000057"},{"id":"T6324","span":{"begin":437,"end":449},"obj":"CHEBI:51686"},{"id":"T6325","span":{"begin":573,"end":578},"obj":"UBERON:0000178"},{"id":"T6326","span":{"begin":606,"end":612},"obj":"NCBITaxon:33208"},{"id":"T6327","span":{"begin":613,"end":618},"obj":"UBERON:0000178"},{"id":"T6328","span":{"begin":712,"end":719},"obj":"CHEBI:46662"},{"id":"T6329","span":{"begin":765,"end":769},"obj":"NCBITaxon:10088"},{"id":"T6330","span":{"begin":882,"end":886},"obj":"NCBITaxon:10088"},{"id":"T6331","span":{"begin":942,"end":949},"obj":"SO:0000704"},{"id":"T6332","span":{"begin":968,"end":977},"obj":"NCBITaxon:1"},{"id":"T6333","span":{"begin":986,"end":992},"obj":"NCBITaxon:33208"},{"id":"T6312","span":{"begin":57,"end":61},"obj":"NCBITaxon:10088"},{"id":"T6313","span":{"begin":77,"end":80},"obj":"PR:000007164"},{"id":"T6314","span":{"begin":85,"end":88},"obj":"PR:000007164"},{"id":"T6315","span":{"begin":99,"end":102},"obj":"PR:000007164"},{"id":"T6316","span":{"begin":109,"end":113},"obj":"NCBITaxon:10088"},{"id":"T6317","span":{"begin":222,"end":225},"obj":"PR:000007164"},{"id":"T6318","span":{"begin":235,"end":238},"obj":"PR:000007164"},{"id":"T6319","span":{"begin":243,"end":250},"obj":"SO:0001023"},{"id":"T6320","span":{"begin":351,"end":355},"obj":"NCBITaxon:10088"},{"id":"T6564","span":{"begin":1120,"end":1125},"obj":"GO:0005675"},{"id":"T6565","span":{"begin":1126,"end":1134},"obj":"MOP:0000780"},{"id":"T6566","span":{"begin":1328,"end":1331},"obj":"PR:000007164"},{"id":"T6567","span":{"begin":1344,"end":1347},"obj":"PR:000007164"},{"id":"T6568","span":{"begin":1365,"end":1368},"obj":"PR:000007164"},{"id":"T6569","span":{"begin":1450,"end":1453},"obj":"PR:000007164"},{"id":"T6570","span":{"begin":1656,"end":1664},"obj":"MOP:0000780"},{"id":"T6571","span":{"begin":1702,"end":1707},"obj":"GO:0005675"},{"id":"T6750","span":{"begin":1868,"end":1882},"obj":"_FRAGMENT"},{"id":"T6751","span":{"begin":1887,"end":1892},"obj":"PR:000008317"},{"id":"T6752","span":{"begin":1887,"end":1892},"obj":"GO:0005675"},{"id":"T6753","span":{"begin":1953,"end":1958},"obj":"NCBITaxon:10088"},{"id":"T6754","span":{"begin":1959,"end":1968},"obj":"UBERON:0000922"},{"id":"T6755","span":{"begin":1969,"end":1980},"obj":"CL:0000057"},{"id":"T6756","span":{"begin":2050,"end":2053},"obj":"PR:000007164"}],"relations":[{"id":"R4647","pred":"_lexicallyChainedTo","subj":"T6751","obj":"T6750"}],"text":"Materials and Methods\n\nDerivation and analysis of mutant mice.\nGeneration of XpdTTD (XPDR722W) and XpdTTD/KO mice has been described previously [21,22]. 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. Chimeric mice and mouse embryonic fibroblasts were generated according to standard procedures. Haematoxylin and eosin staining was performed according to standard procedures. Amino acid analysis was conducted as described in [21]. Blood values were analysed using Animal Blood Counter Vet (ABX Diagnostix, Montpellier, France). Radiographs were taken, and relative bone mineral density was calculated as described in [15]. Mice used in this study were in a 129Ola/C57BL6 mixed background unless noted differently. 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.\n\nUV sensitivity, UV-UDS, UV-RRS, and TFIIH incision/excision activity.\nUV survival, UV-UDS, and UV-RRS assays were performed as described previously [21,30]. 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. 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. For the incision/excision activity assay, recombinant TFIIH was prepared and assayed as described previously [27].\n\nComparative immunofluorescence.\nLatex 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. 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."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T6342","span":{"begin":235,"end":238},"obj":"PR_EXT:000007164"},{"id":"T6343","span":{"begin":243,"end":250},"obj":"SO_EXT:0001023"},{"id":"T6344","span":{"begin":260,"end":269},"obj":"SO_EXT:sequence_alteration_entity_or_process"},{"id":"T6345","span":{"begin":270,"end":278},"obj":"SO_EXT:sequence_coding_function"},{"id":"T6346","span":{"begin":299,"end":310},"obj":"SO_EXT:sequence_alteration_entity_or_process"},{"id":"T6347","span":{"begin":351,"end":355},"obj":"NCBITaxon:10088"},{"id":"T6348","span":{"begin":360,"end":365},"obj":"NCBITaxon:10088"},{"id":"T6349","span":{"begin":366,"end":375},"obj":"UBERON:0000922"},{"id":"T6350","span":{"begin":376,"end":387},"obj":"CL:0000057"},{"id":"T6351","span":{"begin":437,"end":449},"obj":"CHEBI:51686"},{"id":"T6352","span":{"begin":454,"end":459},"obj":"CHEBI_EXT:eosin"},{"id":"T6353","span":{"begin":517,"end":527},"obj":"CHEBI_SO_EXT:amino_acid"},{"id":"T6354","span":{"begin":573,"end":578},"obj":"UBERON:0000178"},{"id":"T6355","span":{"begin":606,"end":612},"obj":"NCBITaxon:33208"},{"id":"T6356","span":{"begin":613,"end":618},"obj":"UBERON:0000178"},{"id":"T6357","span":{"begin":707,"end":711},"obj":"UBERON_EXT:bone_element_or_tissue"},{"id":"T6358","span":{"begin":712,"end":719},"obj":"CHEBI:46662"},{"id":"T6359","span":{"begin":765,"end":769},"obj":"NCBITaxon:10088"},{"id":"T6360","span":{"begin":882,"end":886},"obj":"NCBITaxon:10088"},{"id":"T6361","span":{"begin":942,"end":949},"obj":"SO_EXT:0000704"},{"id":"T6362","span":{"begin":968,"end":977},"obj":"NCBITaxon:1"},{"id":"T6363","span":{"begin":986,"end":992},"obj":"NCBITaxon:33208"},{"id":"T6758","span":{"begin":1868,"end":1882},"obj":"_FRAGMENT"},{"id":"T6759","span":{"begin":1887,"end":1892},"obj":"PR_EXT:000008317"},{"id":"T6760","span":{"begin":1887,"end":1892},"obj":"GO:0005675"},{"id":"T6761","span":{"begin":1953,"end":1958},"obj":"NCBITaxon:10088"},{"id":"T6762","span":{"begin":1959,"end":1968},"obj":"UBERON:0000922"},{"id":"T6763","span":{"begin":1969,"end":1980},"obj":"CL:0000057"},{"id":"T6764","span":{"begin":2010,"end":2014},"obj":"CL_GO_EXT:cell"},{"id":"T6765","span":{"begin":2025,"end":2033},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T6766","span":{"begin":2050,"end":2053},"obj":"PR_EXT:000007164"},{"id":"T6767","span":{"begin":2061,"end":2066},"obj":"CL_GO_EXT:cell"},{"id":"T6768","span":{"begin":2086,"end":2090},"obj":"CL_GO_EXT:cell"},{"id":"T6769","span":{"begin":2185,"end":2193},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T6334","span":{"begin":50,"end":56},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T6335","span":{"begin":57,"end":61},"obj":"NCBITaxon:10088"},{"id":"T6336","span":{"begin":77,"end":80},"obj":"PR_EXT:000007164"},{"id":"T6337","span":{"begin":85,"end":88},"obj":"PR_EXT:000007164"},{"id":"T6338","span":{"begin":99,"end":102},"obj":"PR_EXT:000007164"},{"id":"T6339","span":{"begin":109,"end":113},"obj":"NCBITaxon:10088"},{"id":"T6340","span":{"begin":207,"end":217},"obj":"SO_EXT:engineered_biological_sequence"},{"id":"T6341","span":{"begin":222,"end":225},"obj":"PR_EXT:000007164"},{"id":"T6572","span":{"begin":1120,"end":1125},"obj":"GO:0005675"},{"id":"T6573","span":{"begin":1126,"end":1134},"obj":"MOP:0000780"},{"id":"T6574","span":{"begin":1135,"end":1143},"obj":"SO_EXT:sequence_deletion_process"},{"id":"T6575","span":{"begin":1318,"end":1320},"obj":"SO_EXT:wild_type_entity_or_quality"},{"id":"T6576","span":{"begin":1328,"end":1331},"obj":"PR_EXT:000007164"},{"id":"T6577","span":{"begin":1344,"end":1347},"obj":"PR_EXT:000007164"},{"id":"T6578","span":{"begin":1365,"end":1368},"obj":"PR_EXT:000007164"},{"id":"T6579","span":{"begin":1375,"end":1379},"obj":"CL_GO_EXT:cell"},{"id":"T6580","span":{"begin":1450,"end":1453},"obj":"PR_EXT:000007164"},{"id":"T6581","span":{"begin":1461,"end":1466},"obj":"CL_GO_EXT:cell"},{"id":"T6582","span":{"begin":1623,"end":1627},"obj":"CL_GO_EXT:cell"},{"id":"T6583","span":{"begin":1656,"end":1664},"obj":"MOP:0000780"},{"id":"T6584","span":{"begin":1665,"end":1673},"obj":"SO_EXT:sequence_deletion_process"},{"id":"T6585","span":{"begin":1690,"end":1701},"obj":"GO_SO_EXT:sequence_rearrangement_process"},{"id":"T6586","span":{"begin":1702,"end":1707},"obj":"GO:0005675"},{"id":"T6757","span":{"begin":1807,"end":1816},"obj":"CHEBI_SO_EXT:molecular_label_or_mark_or_tag_process"}],"relations":[{"id":"R4648","pred":"_lexicallyChainedTo","subj":"T6759","obj":"T6758"}],"text":"Materials and Methods\n\nDerivation and analysis of mutant mice.\nGeneration of XpdTTD (XPDR722W) and XpdTTD/KO mice has been described previously [21,22]. 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. Chimeric mice and mouse embryonic fibroblasts were generated according to standard procedures. Haematoxylin and eosin staining was performed according to standard procedures. Amino acid analysis was conducted as described in [21]. Blood values were analysed using Animal Blood Counter Vet (ABX Diagnostix, Montpellier, France). Radiographs were taken, and relative bone mineral density was calculated as described in [15]. Mice used in this study were in a 129Ola/C57BL6 mixed background unless noted differently. 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.\n\nUV sensitivity, UV-UDS, UV-RRS, and TFIIH incision/excision activity.\nUV survival, UV-UDS, and UV-RRS assays were performed as described previously [21,30]. 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. 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. For the incision/excision activity assay, recombinant TFIIH was prepared and assayed as described previously [27].\n\nComparative immunofluorescence.\nLatex 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. 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."}

{"project":"2_test","denotations":[{"id":"17020410-9651581-84795165","span":{"begin":145,"end":147},"obj":"9651581"},{"id":"17020410-9426063-84795166","span":{"begin":148,"end":150},"obj":"9426063"},{"id":"17020410-9651581-84795167","span":{"begin":568,"end":570},"obj":"9651581"},{"id":"17020410-11950998-84795168","span":{"begin":760,"end":762},"obj":"11950998"},{"id":"17020410-9651581-84795169","span":{"begin":1233,"end":1235},"obj":"9651581"},{"id":"17020410-12531012-84795170","span":{"begin":1236,"end":1238},"obj":"12531012"},{"id":"17020410-9651581-84795171","span":{"begin":1525,"end":1527},"obj":"9651581"},{"id":"17020410-12820975-84795172","span":{"begin":1758,"end":1760},"obj":"12820975"},{"id":"17020410-11242112-84795173","span":{"begin":1932,"end":1934},"obj":"11242112"},{"id":"17020410-12393803-84795174","span":{"begin":1935,"end":1937},"obj":"12393803"},{"id":"T86762","span":{"begin":145,"end":147},"obj":"9651581"},{"id":"T68945","span":{"begin":148,"end":150},"obj":"9426063"},{"id":"T30574","span":{"begin":568,"end":570},"obj":"9651581"},{"id":"T65613","span":{"begin":760,"end":762},"obj":"11950998"},{"id":"T19802","span":{"begin":1233,"end":1235},"obj":"9651581"},{"id":"T38157","span":{"begin":1236,"end":1238},"obj":"12531012"},{"id":"T62073","span":{"begin":1525,"end":1527},"obj":"9651581"},{"id":"T15235","span":{"begin":1758,"end":1760},"obj":"12820975"},{"id":"T99220","span":{"begin":1932,"end":1934},"obj":"11242112"},{"id":"T28976","span":{"begin":1935,"end":1937},"obj":"12393803"}],"text":"Materials and Methods\n\nDerivation and analysis of mutant mice.\nGeneration of XpdTTD (XPDR722W) and XpdTTD/KO mice has been described previously [21,22]. 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. Chimeric mice and mouse embryonic fibroblasts were generated according to standard procedures. Haematoxylin and eosin staining was performed according to standard procedures. Amino acid analysis was conducted as described in [21]. Blood values were analysed using Animal Blood Counter Vet (ABX Diagnostix, Montpellier, France). Radiographs were taken, and relative bone mineral density was calculated as described in [15]. Mice used in this study were in a 129Ola/C57BL6 mixed background unless noted differently. 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.\n\nUV sensitivity, UV-UDS, UV-RRS, and TFIIH incision/excision activity.\nUV survival, UV-UDS, and UV-RRS assays were performed as described previously [21,30]. 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. 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. For the incision/excision activity assay, recombinant TFIIH was prepared and assayed as described previously [27].\n\nComparative immunofluorescence.\nLatex 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. 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."}