A p53-independent damage-sensing mechanism that functions as a checkpoint at the G1/S transition in Chinese hamster ovary cells.
In response to a moderate dose of radiation, asynchronous mammalian cell populations rapidly and transiently down-regulate the rate of DNA synthesis to approximately 50% of preirradiation values. We show here that only half of the reduction in overall replication rate can be accounted for by direct inhibition of initiation at origins in S-phase cells. The other half results from the operation of a newly defined cell cycle checkpoint that functions at the G1/S transition. This checkpoint senses damage incurred at any time during the last 2 hr of G1 and effectively prevents entry into the S period. The G1/S and S-phase checkpoints are both p53-independent and, unlike the p53-mediated G1 checkpoint, respond rapidly to radiation, suggesting that they may represent major damage-sensing mechanisms connecting the replication machinery with DNA repair pathways.
Lee
H
H
Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Larner
J M
JM
Hamlin
J L
JL
D000818:Animals; D016466:CHO Cells / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D006224:Cricetinae; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D016196:S Phase; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase