REQUIREMENT OF MISMATCH REPAIR GENES MSH2 AND MSH3 IN THE RAD1-RAD10 PATHWAY OF MITOTIC RECOMBINATION IN SACCHAROMYCES-CEREVISIAE

The RAD1 and RAD10 genes of Saccharomyces cerevisiae are required for nucleotide excision repair and they also act in mitotic recombination. The Rad1-Rad10 complex has a single-stranded DNA endonuclease activit y. Here, we show that the mismatch repair genes MSH2 and MSH3 function in mitotic recombination. For both his3 and his4 duplications, and fo r homologous integration of a linear DNA fragment into the genome, the msh3 Delta mutation has an effect on recombination similar to that of the rad1 Delta and rad10 Delta mutations. The msh2 Delta mutation als o reduces the rate of recombination of the his3 duplication and lowers the incidence of homologous integration of a linear DNA fragment. Epi stasis analyses indicate that MSH2 and MSH3 function in the RAD1-RAD10 recombination pathway, and studies presented here suggest an involvem ent of the RAD1-RAD10 pathway in reciprocal recombination. The possibl e roles of Msh2, Msh3, Rad1, and Rad10 proteins in genetic recombinati on are discussed. Coupling of mismatch binding proteins with the recom binational machinery could be important for ensuring genetic fidelity in the recombination process.