title: DNA polymerase 4 of Saccharomyces cerevisiae is important for accurate repair of methyl-methanesulfonate-induced DNA damage.
abstract: 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 lambda. 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 SK1 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-deficient strain can be rescued by deletion of YKu70. We also show that deletion 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.
authors.affiliation: Department of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06510, USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Sterling
authors.forename: Joann B
authors.initials: JB
authors.lastname: Sweasy
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics; D001483:Base Sequence; D004249:DNA Damage / Q000187:drug effects*; D019951:DNA Polymerase beta; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D000072200:Ku Autoantigen; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; C084892:POL4 protein, S cerevisiae; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen