DIFFERENTIAL-EFFECTS OF THE MISMATCH REPAIR GENES MSH2 AND MSH3 ON HOMEOLOGOUS RECOMBINATION IN SACCHAROMYCES-CEREVISIAE

The products of the yeast mismatch repair genes MSH2 and MSH3 particip ate in the inhibition of genetic recombination between homeologous (di vergent) DNA sequences. In strains deficient for these genes, homeolog ous recombination rates between repeated elements are elevated due to the loss of this inhibition. In this study, the effects of these mutat ions were further analyzed by quantitation of mitotic homeologous reco mbinants as crossovers, gene conversions or exceptional events in wild -type, msh2, msh3 and msh2 msh3 mutant strains. When homeologous seque nces were present as a direct repeat in one orientation, crossovers an d gene conversions were elevated in msh2, msh3 and msh2 msh3 strains. The increases were greater in the msh2 msh3 double mutant than in eith er single mutant. When the order of the homeologous sequences was reve rsed, the msh2 mutation again yielded increased rates of crossovers an d gene conversions. However, in an msh3 strain, gene conversions occur red at higher levels but interchromosomal crossovers were not increase d and intrachromosomal crossovers were reduced relative to wild type. The msh2 msh3 double mutant behaved like the msh2 single mutant in thi s orientation. Control strains harboring homologous duplications were largely but not entirely unaffected in mutant strains, suggesting spec ificity for the mismatched intermediates of homeologous recombination. In all strains, very few (< 10%) recombinants could be attributed to exceptional events. These results suggest that MSH2 and MSH3 can funct ion differentially to control homeologous exchanges.