Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4
Copyright policy )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.
- Wellcome / CRUK Gurdon Institute United Kingdom
- University of Bristol United Kingdom
- University of Cambridge United Kingdom
Poly Adenosine Diphosphate Ribose, Knockout, Messenger, Blotting, Western, 610, Fluorescent Antibody Technique, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Autoantigens, Article, Histones, Mice, Animals, Humans, Immunoprecipitation, Phosphorylation, Mice, Knockout, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Cell Cycle, DNA Helicases, Protein-Serine-Threonine Kinases, Chromatin Assembly and Disassembly, DNA-Binding Proteins, RNA, Tumor Suppressor Protein p53, Western, DNA Damage, Mi-2 Nucleosome Remodeling and Deacetylase Complex
Poly Adenosine Diphosphate Ribose, Knockout, Messenger, Blotting, Western, 610, Fluorescent Antibody Technique, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Autoantigens, Article, Histones, Mice, Animals, Humans, Immunoprecipitation, Phosphorylation, Mice, Knockout, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Cell Cycle, DNA Helicases, Protein-Serine-Threonine Kinases, Chromatin Assembly and Disassembly, DNA-Binding Proteins, RNA, Tumor Suppressor Protein p53, Western, DNA Damage, Mi-2 Nucleosome Remodeling and Deacetylase Complex
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