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. 1999 Oct 7;401(6753):616-20.
doi: 10.1038/44188.

14-3-3Sigma Is Required to Prevent Mitotic Catastrophe After DNA Damage

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14-3-3Sigma Is Required to Prevent Mitotic Catastrophe After DNA Damage

T A Chan et al. Nature. .

Abstract

14-3-3Sigma is a member of a family of proteins that regulate cellular activity by binding and sequestering phosphorylated proteins. It has been suggested that 14-3-3sigma promotes pre-mitotic cell-cycle arrest following DNA damage, and that its expression can be controlled by the p53 tumour suppressor gene. Here we describe an improved approach to the generation of human somatic-cell knockouts, which we have used to generate human colorectal cancer cells in which both 14-3-3sigma alleles are inactivated. After DNA damage, these cells initially arrested in the G2 phase of the cell cycle, but, unlike cells containing 14-3-3sigma, the 14-3-3sigma-/- cells were unable to maintain cell-cycle arrest. The 14-3-3sigma-/- cells died ('mitotic catastrophe') as they entered mitosis. This process was associated with a failure of the 14-3-3sigma-deficient cells to sequester the proteins (cyclin B1 and cdc2) that initiate mitosis and prevent them from entering the nucleus. These results may indicate a mechanism for maintaining the G2 checkpoint and preventing mitotic death.

Comment in

  • Cell cycle. Fools rush in.
    Piwnica-Worms H. Piwnica-Worms H. Nature. 1999 Oct 7;401(6753):535, 537. doi: 10.1038/44029. Nature. 1999. PMID: 10524615 No abstract available.

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