Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-118 |
DRI_Approach |
denotes |
The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions. |
T2 |
119-240 |
DRI_Challenge |
denotes |
MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. |
T3 |
241-503 |
DRI_Challenge |
denotes |
The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. |
T4 |
504-713 |
DRI_Background |
denotes |
Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. |
T5 |
714-802 |
DRI_Approach |
denotes |
Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. |
T6 |
803-879 |
DRI_Approach |
denotes |
We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. |
T7 |
880-990 |
DRI_Approach |
denotes |
We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. |
T8 |
991-1148 |
DRI_Outcome |
denotes |
We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. |
T9 |
1149-1239 |
DRI_Outcome |
denotes |
Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. |
T10 |
1240-1332 |
DRI_Approach |
denotes |
MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. |
T11 |
1333-1482 |
DRI_Outcome |
denotes |
We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. |
T12 |
1483-1608 |
DRI_Approach |
denotes |
This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis. |