Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex.
DNA mismatch repair has a key role in maintaining genomic stability. Defects in mismatch repair cause elevated spontaneous mutation rates and increased instability of simple repetitive sequences, while mutations in human mismatch repair genes result in hereditary nonpolyposis colorectal cancers. Mismatch recognition represents the first critical step of mismatch repair. Genetic and biochemical studies in yeast and humans have indicated a requirement for MSH2-MSH3 and MSH2-MSH6 heterodimers in mismatch recognition. These complexes have, to some extent, overlapping mismatch binding specificities. MLH1 and PMS1 are the other essential components of mismatch repair, but how they function in this process is not known. We have purified the yeast MLH1-PMS1 heterodimer to near homogeneity, and examined its effect on MSH2-MSH3 binding to DNA mismatches. By itself, the MLH1-PMS1 complex shows no affinity for mismatched DNA, but it greatly enhances the mismatch binding ability of MSH2-MSH3.
Habraken
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Y
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.
Sung
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P
Prakash
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L
Prakash
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S
D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000494:pharmacology; D002352:Carrier Proteins; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; D009363:Neoplasm Proteins; C088996:PMS1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein