A NOVEL MUTATION AVOIDANCE MECHANISM DEPENDENT ON SACCHAROMYCES-CEREVISIAE RAD27 IS DISTINCT FROM DNA MISMATCH REPAIR

Mutations in the S. cerevisiae RAD27 (also called RTH1 or YKL510) gene result in a strong mutator phenotype. In this study we show that the majority of the resulting mutations have a structure in which sequence s ranging from 5-108 bp flanked by direct repeats of 3-12 bp are dupli cated. Such mutations have not been previously detected at high freque ncy in the mutation spectra of mutator strains. Epistasis analysis ind icates that RAD27 does not play a major role in MSH2-dependent mismatc h repair. Mutations in RAD27 cause increased rates of mitotic crossing over and are lethal in combination with mutations in RAD51 and RAD52. These observations suggest that the majority of replication errors th at accumulate in rad27 strains are processed by double-strand break re pair, while a smaller percentage are processed by a mutagenic repair p athway. The duplication mutations seen in rad27 mutants occur both in human tumors and as germline mutations in inherited human diseases.