Repair of 8-oxoguanine in Saccharomyces cerevisiae: interplay of DNA repair and replication mechanisms.
8-Oxo-7,8-dihydroguanine (8-oxoG) is produced abundantly in DNA exposed to free radicals and reactive oxygen species. The biological relevance of 8-oxoG has been unveiled by the study of two mutator genes in Escherichia coli, fpg, and mutY. Both genes code for DNA N-glycosylases that cooperate to prevent the mutagenic effects of 8-oxoG in DNA. In Saccharomyces cerevisiae, the OGG1 gene encodes a DNA N-glycosylase/AP lyase, which is the functional homologue of the bacterial fpg gene product. The inactivation of OGG1 in yeast creates a mutator phenotype that is specific for the generation of GC to TA transversions. In yeast, nucleotide excision repair (NER) also contributes to the release of 8-oxoG in damaged DNA. Furthermore, mismatch repair (MMR) mediated by MSH2/MSH6/MLH1 plays a major role in the prevention of the mutagenic effect of 8-oxoG. Indeed, MMR acts as the functional homologue of the MutY protein of E. coli, excising the adenine incorporated opposite 8-oxoG. Finally, the efficient and accurate replication of 8-oxoG by the yeast DNA polymerase eta also prevents 8-oxoG-induced mutagenesis. The aim of this review is to summarize recent literature dealing with the replication and repair of 8-oxoG in Saccharomyces cerevisiae, which can be used as a paradigm for DNA repair in eukaryotes.
Boiteux
Serge
S
CEA, DSV, Département de Radiobiologie et Radiopathologie, CNRS-CEA Radiobiologie Moléculaire et Cellulaire, Fontenay aux Roses, France. boiteux@dsvidf.cea.fr
Gellon
Lionel
L
Guibourt
Nathalie
N
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000595:Amino Acid Sequence; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication / Q000502:physiology*; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics* / Q000633:toxicity; D029968:Escherichia coli Proteins; D005609:Free Radicals; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000502:physiology; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D029968:Escherichia coli Proteins; D005609:Free Radicals; D000080242:8-Hydroxy-2'-Deoxyguanosine; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D003849:Deoxyguanosine