DNA polymerase 4 of Saccharomyces cerevisiae is important for accurate repair of methyl-methanesulfonate-induced DNA damage

The DNA polymerase 4 protein (Pol4) of Saccharomyces cerevisiae is a member of the X family of DNA polymerases whose closest human relative appears to be DNA polymerase X. Results from previous genetic studies conflict over the role of Pol4 in vivo. Here we show that deletion of Pol4 in a diploid strain of the SKI genetic background results in sensitivity to methyl methanesulfonate (MMS). However, deletion of Pol4 in other strain backgrounds and in haploid strains does not yield an observable phenotype. The MMS sensitivity of a Pol4-cleficientstrain can be rescued bydeletion ofYKu70. We also show thattleletion of Pol4 results in a 6- to 14-fold increase in the MMS-induced Mutation frequency and in a significant increase in AT-to-TA transversions. Our studies suggest that Pol4 is critical for accurate repair of DNA lesions induced by MMS.