Gene Symbol: MLH3
Description: mismatch repair protein MLH3
Alias: mismatch repair protein MLH3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Wang T, Kleckner N, Hunter N. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction. Proc Natl Acad Sci U S A. 1999;96:13914-9 pubmed
    ..Mlh1 is the common component of all three complexes, interacting with Pms1, Mlh2, and Mlh3, presumptively as heterodimers...
  2. Flores Rozas H, Kolodner R. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc Natl Acad Sci U S A. 1998;95:12404-9 pubmed
    ..We have investigated the role of MLH3 in mismatch repair...
  3. Oh S, Lao J, Hwang P, Taylor A, Smith G, Hunter N. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell. 2007;130:259-72 pubmed
    ..Sgs1 and procrossover factors, Msh5 and Mlh3, are antagonistic since Sgs1 prevents dHJ formation in msh5 cells and sgs1 mutation alleviates crossover defects of ..
  4. Nishant K, Plys A, Alani E. A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae. Genetics. 2008;179:747-55 pubmed publisher
    ..crossing over in yeast and mammalian meioses involves the mismatch repair protein homologs MSH4-MSH5 and MLH1-MLH3. The MLH3 protein contains a highly conserved metal-binding motif DQHA(X)(2)E(X)(4)E that is found in a subset of ..
  5. Harfe B, Minesinger B, Jinks Robertson S. Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the removal of frameshift intermediates in budding yeast. Curr Biol. 2000;10:145-8 pubmed
    ..We have used two frameshift reversion assays to examine the roles of the yeast Mlh2 and Mlh3 proteins in vivo...
  6. Argueso J, Kijas A, Sarin S, Heck J, Waase M, Alani E. Systematic mutagenesis of the Saccharomyces cerevisiae MLH1 gene reveals distinct roles for Mlh1p in meiotic crossing over and in vegetative and meiotic mismatch repair. Mol Cell Biol. 2003;23:873-86 pubmed
  7. Zakharyevich K, Ma Y, Tang S, Hwang P, Boiteux S, Hunter N. Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Mol Cell. 2010;40:1001-15 pubmed publisher independent of its nuclease activities but requires interaction with the putative endonuclease complex, Mlh1-Mlh3. Thus, the DSB resection and procrossover functions of Exo1 during meiosis involve temporally and biochemically ..
  8. Williams L, Herr A, Preston B. Emergence of DNA polymerase ? antimutators that escape error-induced extinction in yeast. Genetics. 2013;193:751-70 pubmed publisher
    ..synthetic lethality of pol2-4 with alleles that completely abrogate MMR (msh2?, mlh1?, msh3? msh6?, or pms1? mlh3?) but not with partial MMR loss (msh3?, msh6?, pms1?, or mlh3?), indicating that high levels of unrepaired Pol ? ..
  9. Duroc Y, Kumar R, Ranjha L, Adam C, Guérois R, Md Muntaz K, et al. Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion. elife. 2017;6: pubmed publisher
    ..These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations. ..

More Information


  1. Romanova N, Crouse G. Different roles of eukaryotic MutS and MutL complexes in repair of small insertion and deletion loops in yeast. PLoS Genet. 2013;9:e1003920 pubmed publisher
    ..MutS? is present in many eukaryotic organisms, but not in prokaryotes. We suggest that the biased repair of deletion mispairs may reflect a critical eukaryotic function of MutS? in mismatch repair. ..
  2. Ranjha L, Anand R, Cejka P. The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions. J Biol Chem. 2014;289:5674-86 pubmed publisher
    MutL?, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination...
  3. Rogacheva M, Manhart C, Chen C, Guarné A, SURTEES J, Alani E. Mlh1-Mlh3, a meiotic crossover and DNA mismatch repair factor, is a Msh2-Msh3-stimulated endonuclease. J Biol Chem. 2014;289:5664-73 pubmed publisher
    ..requiring Sgs1 helicase, Exo1, and a putative endonuclease activity encoded by the DNA mismatch repair factor Mlh1-Mlh3. We purified Mlh1-Mlh3 and showed that it is a metal-dependent and Msh2-Msh3-stimulated endonuclease that makes ..
  4. Su X, Freudenreich C. Cytosine deamination and base excision repair cause R-loop-induced CAG repeat fragility and instability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2017;114:E8392-E8401 pubmed publisher
    ..Surprisingly, the MutL? (Mlh1/Mlh3) endonuclease caused R-loop-dependent CAG fragility, defining an alternative function for this complex...
  5. Chakraborty P, Pankajam A, Lin G, Dutta A, Krishnaprasad N, Tekkedil M, et al. Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces cerevisiae Meiosis. G3 (Bethesda). 2017;7:1511-1524 pubmed publisher
    ..previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3? and enhanced in a meiotic checkpoint mutant pch2? by up to twofold at specific chromosomal loci, but ..
  6. Copsey A, Tang S, Jordan P, Blitzblau H, Newcombe S, Chan A, et al. Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions. PLoS Genet. 2013;9:e1004071 pubmed publisher
  7. Sonntag Brown M, Lim E, Chen C, Nishant K, Alani E. Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast. G3 (Bethesda). 2013;3:9-22 pubmed publisher
    ..In baker's yeast, two heterodimeric complexes, Msh4-Msh5 and Mlh1-Mlh3, act in meiosis to promote interference-dependent crossing over...
  8. Voelkel Meiman K, Cheng S, Morehouse S, MacQueen A. Synaptonemal Complex Proteins of Budding Yeast Define Reciprocal Roles in MutS?-Mediated Crossover Formation. Genetics. 2016;203:1091-103 pubmed publisher
    ..The latter class directly or indirectly limits MutS?-mediated crossovers along meiotic chromosomes. Our findings illustrate how reciprocal roles in crossover recombination can be simultaneously linked to the SC structure. ..
  9. Al Sweel N, Raghavan V, Dutta A, Ajith V, Di Vietro L, Khondakar N, et al. mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide. PLoS Genet. 2017;13:e1006974 pubmed publisher
    Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR)...
  10. Wang T, Kung W. Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in meiotic yeast cells. Biochem Biophys Res Commun. 2002;296:949-53 pubmed
    ..cerevisia encodes four mismatch repair MutL proteins and these proteins form three heterocomplexes: Mlh1-Mlh2, Mlh1-Mlh3, and Mlh1-Pms1...
  11. Stone J, Petes T. Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics. 2006;173:1223-39 pubmed
    ..We also found that the frequency and position of local double-strand DNA breaks affect the ratio of mismatch repair events that lead to gene conversion vs. restoration of Mendelian segregation. ..