THE SACCHAROMYCES-CEREVISIAE RAD9, RAD17, RAD24 AND MEC3 GENES ARE REQUIRED FOR TOLERATING IRREPARABLE, ULTRAVIOLET-INDUCED DNA-DAMAGE

In wild-type Saccharomyces cerevisiae, a checkpoint slows the rate of progression of an ongoing S phase in response to exposure to a DNA-alk ylating agent. Mutations that eliminate S phase regulation also confer sensitivity to alkylating agents, leading us to suggest that, by regu lating the S phase rate, cells are either better able to repair or bet ter able to replicate damaged DNA. In this study, we determine the eff ects of mutations that impair S phase regulation on the ability of exc ision repair-defective cells to replicate irreparably UV-damaged DNA. We assay survival after UV irradiation, as well as the genetic consequ ences of replicating a damaged template, namely mutation and sister ch romatid exchange induction. We find that RAD9, RAD17, RAD24, and MEC3 are required for UV-induced (although not spontaneous) mutagenesis, an d that RAD9 and RAD17 (but not REV3, RAD24, and MEC3) are required for maximal induction of replication-dependent sister chromatid exchange. Therefore, checkpoint genes not only control cell cycle progression i n response to damage, but also play a role in accommodating DNA damage during replication.