The human intra-S checkpoint response to UVC-induced DNA damage.
The intra-S checkpoint response to 254 nm light (UVC)-induced DNA damage appears to have dual functions to slow the rate of DNA synthesis and stabilize replication forks that become stalled at sites of UVC-induced photoproducts in DNA. These functions should provide more time for repair of damaged DNA before its replication and thereby reduce the frequencies of mutations and chromosomal aberrations in surviving cells. This review tries to summarize the history of discovery of the checkpoint, the current state of understanding of the biological features of intra-S checkpoint signaling and its mechanisms of action with a focus primarily on intra-S checkpoint responses in human cells. The differences in the intra-S checkpoint responses to UVC and ionizing radiation-induced DNA damage are emphasized. Evidence that [6-4]pyrimidine-pyrimidone photoproducts in DNA trigger the response is discussed and the relationships between cellular responses to UVC and the molecular dose of UVC-induced DNA damage are briefly summarized. The role of the intra-S checkpoint response in protecting against solar radiation carcinogenesis remains to be determined.
Department of Pathology and Laboratory Medicine, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA. wkarlk@med.unc.edu
William K
WK
Kaufmann
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000528:radiation effects; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000378:metabolism; D012093:Replicon; D016196:S Phase / Q000528:radiation effects*; D015398:Signal Transduction; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D011494:Protein Kinases