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.
Polo
Sophie E
SE
Department of Biochemistry, The Gurdon Institute, University of Cambridge, Cambridge, UK.
Kaidi
Abderrahmane
A
Baskcomb
Linda
L
Galanty
Yaron
Y
Jackson
Stephen P
SP
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D064007:Ataxia Telangiectasia Mutated Proteins; D001324:Autoantigens; D018797:Cell Cycle Proteins; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D006657:Histones; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D011064:Poly Adenosine Diphosphate Ribose; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C115323:CHD4 protein, human; C576324:ATM protein, human; C576325:Atm protein, mouse; C509277:Mi-2beta protein, mouse; C475961:gamma-H2AX protein, mouse