Editors' ChoiceCell Biology

Dealing with DNA Damage

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Science's STKE  17 Oct 2006:
Vol. 2006, Issue 357, pp. tw359
DOI: 10.1126/stke.3572006tw359

For an organism to remain healthy, cells with damaged DNA must either pause in the cell cycle for a repair job or succumb to elimination by apoptosis. Huang et al. provide a mechanism through which cells with genomic damage may switch between these alternative fates. DNA damage activates a checkpoint signaling mechanism that arrests the cell cycle in part by inhibiting activity of cyclin-dependent kinase 2 (CDK2). The authors now find that CDK2 may also couple to the machinery controlling cell death. Normally, the transcription factor FOXO1 is phosphorylated by CDK2. In cells with extensive DNA damage, reduced phosphorylation of FOXO1 allows its translocation to the nucleus, where it enhances expression of apoptosis-inducing genes.

H. Huang, K. M. Regan, Z. Lou, J. Chen, D. J. Tindall, CDK-2 dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science 314, 294-297 (2006). [Abstract] [Full Text]

J. Bartek, J. Lukas, Balancing life-or-death decisions. Science 314, 261-262 (2006). [Abstract] [Full Text]

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