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

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.
Mesh Terms:
Animals, Autoantigens, Blotting, Western, Cell Cycle, Cell Cycle Proteins, Chromatin Assembly and Disassembly, DNA Damage, DNA Helicases, DNA-Binding Proteins, Fluorescent Antibody Technique, Histones, Humans, Immunoprecipitation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Mice, Knockout, Phosphorylation, Poly Adenosine Diphosphate Ribose, Protein-Serine-Threonine Kinases, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p53, Tumor Suppressor Proteins
EMBO J.
Date: Sep. 15, 2010
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