Silent repair accounts for cell cycle specificity in the signaling of oxidative DNA lesions.
Reactive oxygen species are the most important source of DNA lesions in aerobic organisms, but little is known about the activation of the DNA checkpoints in response to oxidative stress. We show that treatment of yeast cells with sublethal concentrations of hydrogen peroxide induces a Mec1-dependent phosphorylation of Rad53 and a Rad53-dependent cell cycle delay specifically during S phase. The lack of Rad53 phosphorylation after hydrogen peroxide treatment in the G1 and G2 phases is due to the silent repair of oxidative DNA lesions produced at these stages by the base excision repair (BER) pathway. Only the disruption of the BER pathway and the accumulation and/or treatment of DNA intermediates by alternative repair pathways reveal the existence of primary DNA lesions induced at all phases of the cell cycle by hydrogen peroxide. Our data illustrate both the concept of silent repair of DNA damage and the high sensitivity of S-phase cells to hydrogen peroxide.
Leroy
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Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, F-91191 Gif-sur-Yvette Cedex, France.
Mann
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Marsolier
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D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004271:DNA, Fungal / Q000187:drug effects / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species / Q000502:physiology; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013698:Templates, Genetic
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D009838:Oligodeoxyribonucleotides; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae