Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis

Mutat Res. 1994 Nov;315(3):281-93. doi: 10.1016/0921-8777(94)90039-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA, Fungal / radiation effects
  • DNA-Binding Proteins / genetics*
  • Fungal Proteins / genetics*
  • Genes, Fungal / radiation effects
  • Genes, Suppressor / genetics
  • Molecular Sequence Data
  • Mutagenesis*
  • Point Mutation / genetics
  • RNA, Transfer / genetics
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion / physiology
  • Ultraviolet Rays*

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD18 protein, S cerevisiae
  • RAD52 protein, S cerevisiae
  • Rad52 DNA Repair and Recombination Protein
  • Saccharomyces cerevisiae Proteins
  • RNA, Transfer