Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis.
In eukaryotes, homologs of the bacterial MutS and MutL proteins function in DNA mismatch repair and recombination pathways. The mutL homolog MLH1 is required for nuclear mismatch repair. Previously, cytological analysis of MLH1-deficient mice has implied a role for Mlh1 in crossing-over during meiosis. Here we demonstrate that Saccharomyces cerevisiae diploids containing a deletion of MLH1 have reduced crossing-over in addition to a deficiency in the repair of mismatched DNA during meiosis. Absence of either of the meiosis-specific mutS homologs Msh4 or Msh5 results in a similar reduction in crossing-over. Analysis of an mlh1 msh4 double mutant suggests that both genes act in the same pathway to promote crossing-over. All genetic markers analyzed in mlh1 mutants display elevated frequencies of non-Mendelian segregation. Most of these events are postmeiotic segregations that represent unrepaired heteroduplex. These data suggest that either restorational repair is frequent or heteroduplex tracts are shorter in wild-type cells. Comparison of mlh1 segregation data with that of pms1, msh2, msh3, and msh6 mutants show that the ability to promote crossing-over is unique to MLH1. Taken together these observations indicate that both crossing-over and gene conversion require MutS and MutL functions and that Mlh1 represents an overlap between these two pathways. Models of Mlh1 function are discussed.
Hunter
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Yeast Genetics, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Borts
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RH
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D003434:Crossing Over, Genetic; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D007621:Karyotyping; D008540:Meiosis; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D013172:Spores, Fungal
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; C091158:MSH4 protein, S cerevisiae; C074770:MutL protein, E coli; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051719:MutS DNA Mismatch-Binding Protein; C497175:MutS protein, E coli