Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation.
Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.
Suzuki
Keiji
K
Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan. kzsuzuki@nagasaki-u.ac.jp
Kodama
Seiji
S
Watanabe
Masami
M
D000818:Animals; D034961:Antigens, Nuclear / Q000502:physiology*; D064007:Ataxia Telangiectasia Mutated Proteins; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000502:physiology; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D019457:Chromosome Breakage / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects*; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins / Q000502:physiology; D000076105:X-ray Repair Cross Complementing Protein 1
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; C000606512:Xrcc5 protein, mouse; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen