Shedding light on the DNA damage checkpoint.
DNA damage checkpoint genes are required to restrain cell cycle progression during DNA repair and to maintain chromosome stability. Checkpoint mutants are highly sensitive to killing by UV light, so the responses mediated by these genes are likely to be essential for survival during exposure to solar radiation. Yet it is still unclear exactly how checkpoint responses coordinate the cell cycle with DNA repair in the presence of UV lesions. At high doses, the UV response shares features with the ionizing radiation response, such as G1/S and G2/M checkpoints. At lower doses, only a postreplication checkpoint is evident. In this perspective we attempt to reconcile these observations and address their physiological meaning, with an emphasis on insights gained from direct cell-cycle measurements and recent studies in yeast.
Callegari
A John
AJ
Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. tkelly@mskcc.org
Kelly
Thomas J
TJ
D000818:Animals; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology* / Q000528:radiation effects*; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D004261:DNA Replication / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D014466:Ultraviolet Rays