title: DNA base excision repair and nucleotide excision repair synergistically contribute to survival of stationary-phase cells of the fission yeast Schizosaccharomyces pombe.
abstract: Defects of genome maintenance may causally contribute to aging. In general, base excision repair (BER) is involved in the repair of subtle base lesions and AP sites, and bulky helix-distorting lesions are restored by nucleotide excision repair (NER). Here, we measured the chronological lifespan (CLS) of BER- and NER-deficient mutants of the fission yeast Schizosaccharomyces pombe, and observed the aging process of cells. The CLS of the nth1 (gene for DNA glycosylase/AP lyase) mutant and the rad16 (a homolog of human XPF) mutant were slightly shorter than that of the wild-type (WT) strain. However, survival of the nth1Δ rad16Δ double mutant was significantly reduced after entry into the stationary phase. Deletion of rad16 in an AP endonuclease mutant apn2Δ also accelerated chronological aging. These results indicate that BER and NER synergistically contribute to genome maintenance in non-dividing cells. Reactive oxygen species (ROS) accumulated in cells during the stationary phase, and nth1Δ rad16Δ cells produced more ROS than WT cells. High mutation frequencies and nuclear DNA fragmentation were observed in nth1Δ rad16Δ stationary-phase cells concurrent with apoptotic-like cell death. Calorie restriction significantly reduced the level of ROS in the stationary phase and extended the CLS of nth1Δ rad16Δ cells. Therefore, ROS production critically affects the survival of the DNA repair mutant during chronological aging.
authors.affiliation: Department of Biochemistry, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Senoo
authors.affiliation: Department of Biochemistry, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Department of Biochemistry, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D029702:Schizosaccharomyces pombe Proteins
keywords: DNA repair; Schizosaccharomyces pombe; chronological lifespan; oxidative DNA damage; reactive oxygen species