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Mammalian G1- and S-phase checkpoints in response to DNA damage

2001; Elsevier BV; Volume: 13; Issue: 6 Linguagem: Inglês

10.1016/s0955-0674(00)00280-5

1879-0410

Jiří Bártek, Jiří Lukáš,

Genomics and Chromatin Dynamics

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.