title: Base analog 6-N-hydroxylaminopurine mutagenesis in the yeast Saccharomyces cerevisiae is controlled by replicative DNA polymerases.
abstract: Genetic control of mutagenesis by the base analog 6-N-hydroxylaminopurine (HAP) was studied in a set of isogenic yeast strains carrying null or point mutations in DNA repair and replication genes. Null alleles of the PMS1, RAD6, REV3 and RAD52 genes did not affect HAP mutagenesis. Defects in 3'- > 5' exonucleases associated with DNA polymerases epsilon and delta led to 2- to 3-fold increases in HAP-induced forward Can(r) mutant frequency. A similar increase was observed for FOAr mutants but only in the strain with a defective exonuclease of the polymerase epsilon (mutation pol2-4). The polymerase epsilon mutations, pol2-9 and pol2-18, which lead to temperature-sensitivity, and pol2-1 (insertion of URA3 at the position coding for amino acid 1134 in the POL2 gene) substantially reduced HAP mutagenesis. The polymerase delta mutation, cdc2-2, slightly reduced HAP mutagenesis. Enhanced proofreading was not the cause of the antimutator effect in the pol2-18 bearing strain, inasmuch as antimutator effect was observed in the pol2-4,18 mutant strain lacking proofreading. From the data obtained, we conclude that both DNA polymerase epsilon and delta participate in mutation generation by HAP.
authors.affiliation: Department of Genetics, Sankt-Petersburg University, Russia.
authors.forename: P V
authors.initials: PV
authors.lastname: Shcherbakova
authors.forename: V N
authors.initials: VN
authors.lastname: Noskov
authors.forename: M R
authors.initials: MR
authors.lastname: Pshenichnov
authors.forename: Y I
authors.initials: YI
authors.lastname: Pavlov
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics; D008025:Ligases / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D010957:Plasmids; D017354:Point Mutation; D051721:Rad52 DNA Repair and Recombination Protein; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009153:Mutagens; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C032610:6-N-hydroxylaminopurine; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase; C092602:REV3 protein, S cerevisiae; D008025:Ligases; D000225:Adenine