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Cancer Metastasis Rev. 1995 Mar;14(1):17-29.

Cell cycle regulation in response to DNA damage in mammalian cells: a historical perspective.

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Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, USA.

Erratum in

  • Cancer Metastasis Rev 1995 Sep;14(3):253-4.


Cell cycle delay has long been known to occur in mammalian cells after exposure to DNA-damaging agents. It has been hypothesized that the function of this delay is to provide additional time for repair of DNA before the cell enters critical periods of the cell cycle, such as DNA synthesis in S phase or chromosome condensation in G2 phase. Recent evidence that p53 protein is involved in the delay in G1 in response to ionizing radiation has heightened interest in the importance of cell cycle delay, because mutations in p53 are commonly found in human cancer cells. Because mammalian cells defective in p53 protein show increased genomic instability, it is tempting to speculate that the instability is due to increased chromosome damage resulting from the lack of a G1 delay. Although this appears at first glance to be a highly plausible explanation, a review of the research performed on cell cycle regulation and DNA damage in mammalian cells provides little evidence to support this hypothesis. Studies involving cells treated with caffeine, cells from humans with the genetic disease ataxia telangiectasia, and cells that are deficient in p53 show no correlation between G1 delay and increased cell killing or chromosome damage in response to ionizing radiation. Instead, G1 delay appears to be only one aspect of a complex cellular response to DNA damage that also includes delays in S phase and G2 phase, apoptosis and chromosome repair. The exact mechanism of the genomic instability associated with p53, and its relationship to the failure to repair DNA before progression through the cell cycle, remains to be determined.

[Indexed for MEDLINE]

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