Mammalian G1- and S-phase checkpoints in response to DNA damage.
The ability to preserve genomic integrity is a fundamental feature of life. Recent findings regarding the molecular basis of the cell-cycle checkpoint responses of mammalian cells to genotoxic stress have converged into a two-wave concept of the G1 checkpoint, and shed light on the so-far elusive intra-S-phase checkpoint. Rapidly operating cascades that target the Cdc25A phosphatase appear central in both the initiation wave of the G1 checkpoint (preceding the p53-mediated maintenance wave) and the transient intra-S-phase response. Multiple links between defects in the G1/S checkpoints, genomic instability and oncogenesis are emerging, as are new challenges and hopes raised by this knowledge.
Bartek
J
J
Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark. bartek@biobase.dk
Lukas
J
J
D000818:Animals; D004249:DNA Damage; D005544:Forecasting; D016193:G1 Phase; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics; D011494:Protein Kinases / Q000502:physiology; D016196:S Phase; D014157:Transcription Factors / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D020687:cdc25 Phosphatases / Q000502:physiology
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D020687:cdc25 Phosphatases