title: Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis.
abstract: Experimental evidence indicates that although the Saccharomyces cerevisiae RAD18 and RAD52 genes are not required for nucleotide excision repair, they function in the processing of UV-induced DNA damage in yeast. Conflicting statements regarding the UV mutability of strains deleted for RAD18 prompted us to re-examine the influence of RAD18, and RAD52, on UV mutagenesis. To do so, we characterized mutations induced by UV in SUP4-o, a yeast suppressor tRNA gene. SUP4-o was maintained on a plasmid in isogenic strains that either carried one of two different rad18 deletions (rad18 delta) or had RAD52 disrupted. Both rad18 deletions decreased the frequency of UV-induced SUP4-o mutations to levels close to those for spontaneous mutagenesis in the rad18 delta backgrounds, and prevented a net increase in mutant yield. A detailed analysis of mutations isolated after UV irradiation of one of the rad18 delta strains uncovered little evidence of the specificity features typical for UV mutagenesis in the isogenic repair-proficient (RAD) parent (e.g., predominance of G.C-->A.T transitions). Evidently, UV induction of SUP4-o mutations is highly dependent on the RAD18 gene. Compared to the RAD strain, disruption of RAD52 reduced the frequency and yield of UV mutagenesis by about two-thirds. Closer inspection revealed that 80% of this reduction was due to a decrease in the frequency of G.C-->A.T transitions. In addition, there were differences in the distributions and site specificities of single base-pair substitutions. Thus, RAD52 also participates in UV mutagenesis of a plasmid-borne gene in yeast, but to a lesser extent than RAD18.
authors.affiliation: Microbiology Department, University of Manitoba, Winnipeg, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Armstrong
authors.forename: D N
authors.initials: DN
authors.lastname: Chadee
authors.forename: B A
authors.initials: BA
authors.lastname: Kunz
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D005800:Genes, Fungal / Q000528:radiation effects; D016153:Genes, Suppressor / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017354:Point Mutation / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C063607:RAD18 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer