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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Autoantigens / genetics
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Autoantigens / metabolism*
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Blotting, Western
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Cell Cycle / physiology*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Chromatin Assembly and Disassembly*
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DNA Damage*
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DNA Helicases / genetics
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DNA Helicases / metabolism*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Fluorescent Antibody Technique
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Histones / physiology
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Humans
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Immunoprecipitation
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Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics
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Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
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Mice
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Mice, Knockout
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Phosphorylation
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Poly Adenosine Diphosphate Ribose / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Suppressor Protein p53 / physiology
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Autoantigens
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CHD4 protein, human
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Cell Cycle Proteins
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DNA-Binding Proteins
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H2AX protein, mouse
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Histones
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RNA, Messenger
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Poly Adenosine Diphosphate Ribose
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Atm protein, mouse
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Protein Serine-Threonine Kinases
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Mi-2beta protein, mouse
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DNA Helicases