title: Influence of DNA repair defects (rad1, rad52) on nitrogen mustard mutagenesis in yeast.
abstract: Nitrogen mustard (HN2) mutagenesis of a plasmid-borne copy of the Saccharomyces cerevisiae SUP4-o gene was examined in a repair-proficient yeast strain and isogenic derivatives defective for excision (rad1) or DNA double-strand break (rad52) repair. The excision repair deficiency sensitized the cells to killing by HN2 and abolished mutation induction. Inactivation of RAD52 had no influence on the lethality of HN2 treatment but diminished the induced mutation frequency by 50% at all doses tested. DNA sequence analysis of HN2-induced SUP4-o mutations suggested that RAD52 contributed to the production of basepair substitutions at G.C sites. The rad52 defect appeared to alter the distribution of G.C-->A.T transitions in SUP4-o relative to the distribution for the wild-type strain. This difference did not seem to be due to an effect of RAD52 on the relative fractions of HN2-induced transitions at localized (flanked by A.T pairs) or contiguous (flanked by at least one G.C pair) G.C sites but instead to an influence on the strand specificity of HN2 mutagenesis. In the repair-proficient strain, the transitions showed a small bias for sites having the guanine on the transcribed strand and this preference was eliminated by inactivation of RAD52.
authors.affiliation: Microbiology Department, University of Manitoba, Winnipeg, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Mis
authors.forename: B A
authors.initials: BA
authors.lastname: Kunz
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D004260:DNA Repair; D004251:DNA Transposable Elements; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D008466:Mechlorethamine / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D004251:DNA Transposable Elements; D004271:DNA, Fungal; D008466:Mechlorethamine