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EMBO J. 2010 Sep 15;29(18):3130-9. doi: 10.1038/emboj.2010.188. Epub 2010 Aug 6.

Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4.

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1
Department of Biochemistry, The Gurdon Institute, University of Cambridge, Cambridge, UK.

Abstract

The chromatin remodelling factor chromodomain helicase DNA-binding protein 4 (CHD4) is a catalytic subunit of the NuRD transcriptional repressor complex. Here, we reveal novel functions for CHD4 in the DNA-damage response (DDR) and cell-cycle control. We show that CHD4 mediates rapid poly(ADP-ribose)-dependent recruitment of the NuRD complex to DNA-damage sites, and we identify CHD4 as a phosphorylation target for the apical DDR kinase ataxia-telangiectasia mutated. Functionally, we show that CHD4 promotes repair of DNA double-strand breaks and cell survival after DNA damage. In addition, we show that CHD4 acts as an important regulator of the G1/S cell-cycle transition by controlling p53 deacetylation. These results provide new insights into how the chromatin remodelling complex NuRD contributes to maintaining genome stability.

PMID:
20693977
PMCID:
PMC2944064
DOI:
10.1038/emboj.2010.188
[Indexed for MEDLINE]
Free PMC Article

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