UV irradiation induces a postreplication DNA damage checkpoint.
Eukaryotic cells irradiated with high doses of UV exhibit cell-cycle responses referred to as G(1)/S, intraS, and G(2)/M checkpoints. After a moderate UV dose that approximates sunlight exposure and is lethal to fission yeast checkpoint mutants, we found unexpectedly that these cell-cycle responses do not occur. Instead, cells at all stages of the cell cycle carry lesions into S phase and delay cell-cycle progression for hours after the completion of bulk DNA synthesis. Both DNA replication and the checkpoint kinase, Chk1, are required to generate this cell-cycle response. UV-irradiation of Deltachk1 cells causes chromosome damage and loss of viability only after cells have replicated irradiated DNA and entered mitosis. These data suggest that an important physiological role of the cell-cycle response to UV is to provide time for postreplication repair.
Callegari
A John
AJ
Program in Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Kelly
Thomas J
TJ
D002453:Cell Cycle / Q000235:genetics* / Q000528:radiation effects*; D000071877:Checkpoint Kinase 1; D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics* / Q000528:radiation effects*; D004271:DNA, Fungal / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D029702:Schizosaccharomyces pombe Proteins; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605873:Chk1 protein, S pombe