Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to DNA repair defects.
While the Ku complex, comprised of Ku70 and Ku80, is primarily involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type or Ku80-null (Ku80(-/-)) mice with various stress agents revealed that hydrogen peroxide (H(2)O(2)) was markedly more cytotoxic for Ku80(-/-) MEFs and led to their long-term accumulation in the G2 phase. This differential response was not due to differences in DNA repair, since H(2)O(2)-triggered DNA damage was repaired with comparable efficiency in both Wt and Ku80(-/-) MEFs, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and G2-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.
Arrington
E D
ED
Laboratory of Biological Chemistry, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Caldwell
M C
MC
Kumaravel
T S
TS
Lohani
A
A
Joshi
A
A
Evans
M K
MK
Chen
H T
HT
Nussenzweig
A
A
Holbrook
N J
NJ
Gorospe
M
M
D000818:Animals; D034961:Antigens, Nuclear; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000502:physiology; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005609:Free Radicals; D016195:G2 Phase / Q000187:drug effects*; D005720:Gamma Rays; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000502:physiology
D034961:Antigens, Nuclear; D016213:Cyclins; D004268:DNA-Binding Proteins; D005609:Free Radicals; D009687:Nuclear Proteins; D006861:Hydrogen Peroxide; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen