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First published online April 5, 2005

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STATionary after DNA damage

To maintain genomic integrity, eukaryotic cells have cell-cycle checkpoints, signal transduction pathways that detect DNA damage and halt the cell cycle until the damage is repaired. Now Anastasis Stephanou and colleagues report that the signalling molecule STAT-1 (signal transducer and activator of transcription 1) facilitates the ATM-mediated checkpoints induced after DNA damage caused by ionizing radiation (see p. 1629). STAT-1, a possible tumour suppressor, plays a role in interferon-mediated growth arrest and apoptosis. To discover how STAT-1 inhibits cell growth, the authors examine its role in DNA-damage response pathways in mouse and human cells. They show that STAT-1-deficient cells have defects in the intra-S and G2-M checkpoint responses to DNA damage. These defects include reduced phosphorylation of the checkpoint kinase Chk2 and of some downstream targets of the ATM kinase. The expression of MDC1 and 53BP1, two proteins required for ATM-mediated checkpoints, is also reduced in STAT-1-deficient cells; enforced MDC1 expression restores ATM-mediated phosphorylation of downstream substrates. The authors conclude that STAT-1 plays a crucial role in modulating cell-cycle-checkpoint responses after DNA damage.

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Related articles in JCS:

STAT-1 facilitates the ATM activated checkpoint pathway following DNA damage

Paul A. Townsend, Mark S. Cragg, Sean M. Davidson, James McCormick, Sean Barry, Kevin M. Lawrence, Richard A. Knight, Michael Hubank, Phang-Lang Chen, David S. Latchman, and Anastasis Stephanou
JCS 2005 118: 1629-1639. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?