title: The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose).
abstract: Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNA-damage responses through its N-terminal region in a poly(ADP-ribose) polymerase-dependent manner. We have identified and determined the structure of a stable domain (CHD4-N) in this N-terminal region. The-fold consists of a four-α-helix bundle with structural similarity to the high mobility group box, a domain that is well known as a DNA binding module. We show that the CHD4-N domain binds with higher affinity to poly(ADP-ribose) than to DNA. We also show that the N-terminal region of CHD4, although not CHD4-N alone, is essential for full nucleosome remodeling activity and is important for localizing CHD4 to sites of DNA damage. Overall, these data build on our understanding of how CHD4-NuRD acts to regulate gene expression and participates in the DNA-damage response.
authors.affiliation: From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia, ana.silva@sydney.edu.au.
authors.forename: Ana P G
authors.initials: AP
authors.lastname: Silva
authors.affiliation: Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, and.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Ryan
authors.affiliation: The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Galanty
authors.affiliation: From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia.
authors.forename: Jason K K
authors.initials: JK
authors.lastname: Low
authors.affiliation: From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia.
authors.forename: Marylene
authors.initials: M
authors.lastname: Vandevenne
authors.affiliation: The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
authors.affiliation: From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia, joel.mackay@sydney.edu.au.
authors.forename: Joel P
authors.initials: JP
authors.lastname: Mackay
mesh_terms: D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D057809:HEK293 Cells; D024742:HMG-Box Domains; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D009707:Nucleosomes; D010455:Peptides; D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: CHD4; DNA binding protein; DNA damage; HMG-box; chromatin remodeling; nucleosome; nucleosome remodeling deacetylase (NuRD); poly(ADP-ribose)