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J Biol Chem. 2016 Jan 8;291(2):924-38. doi: 10.1074/jbc.M115.683227. Epub 2015 Nov 12.

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).

Author information

1
From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia, ana.silva@sydney.edu.au.
2
Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, and.
3
The Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
4
From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia.
5
From the School of Molecular Bioscience, The University of Sydney, New South Wales 2006, Australia, joel.mackay@sydney.edu.au.

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.

KEYWORDS:

CHD4; DNA binding protein; DNA damage; HMG-box; chromatin remodeling; nucleosome; nucleosome remodeling deacetylase (NuRD); poly(ADP-ribose)

PMID:
26565020
PMCID:
PMC4705410
DOI:
10.1074/jbc.M115.683227
[Indexed for MEDLINE]
Free PMC Article

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