title: Yeast base excision repair: interconnections and networks.
abstract: The removal of oxidative base damage from the genome of Saccharomyces cerevisiae is thought to occur primarily via the base excision repair (BER) pathway in a process initiated by several DNA N-glycosylase/AP lyases. We have found that yeast strains containing simultaneous multiple disruptions of BER genes are not hypersensitive to killing by oxidizing agents, but exhibit a spontaneous hyperrecombinogenic (hyper-rec) and mutator phenotype. The hyper-rec and mutator phenotypes are further enhanced by elimination of the nucleotide excision repair (NER) pathway. Furthermore, elimination of either the lesion bypass (REV3-dependent) or recombination (RAD52-dependent) pathway results in a further, specific enhancement of the hyper-rec or mutator phenotypes, respectively. Sensitivity (cell killing) to oxidizing agents is not observed unless multiple pathways are eliminated simultaneously. These data suggest that the BER, NER, recombination, and lesion bypass pathways have overlapping specificities in the removal of, or tolerance to, exogenous or spontaneous oxidative DNA damage in S. cerevisiae. Our results also suggest a physiological role for the AP lyase activity of certain BER N-glycosylases in vivo.
authors.affiliation: Departments of Biochemistry and Radiation Oncology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Doetsch
authors.forename: N J
authors.initials: NJ
authors.lastname: Morey
authors.forename: R L
authors.initials: RL
authors.lastname: Swanson
authors.forename: S
authors.initials: S
authors.lastname: Jinks-Robertson
mesh_terms: D019757:Carbon-Oxygen Lyases / Q000502:physiology; D004249:DNA Damage; D045647:DNA Glycosylases; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000502:physiology; D004259:DNA-Directed DNA Polymerase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004720:Endonucleases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D008957:Models, Genetic; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D010641:Phenotype; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016877:Oxidants; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D004259:DNA-Directed DNA Polymerase; C092602:REV3 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; D043223:Deoxyribonuclease IV (Phage T4-Induced); C083274:Apn1 protein, S cerevisiae; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C101825:NTG1 protein, S cerevisiae; C116827:NTG2 protein, S cerevisiae; D011088:DNA Ligases; D045643:DNA Repair Enzymes