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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).


Type

Article

Change log

Authors

Silva, Ana PG 
Ryan, Daniel P 
Low, Jason KK 
Vandevenne, Marylene 

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.

Description

Keywords

CHD4, DNA binding protein, DNA damage, HMG-box, chromatin remodeling, nucleosome, nucleosome remodeling deacetylase (NuRD), poly(ADP-ribose), Amino Acid Sequence, Autoantigens, Chromatin Assembly and Disassembly, Conserved Sequence, DNA, DNA Breaks, Double-Stranded, DNA Damage, HEK293 Cells, HMG-Box Domains, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Models, Molecular, Molecular Sequence Data, Nucleosomes, Peptides, Poly Adenosine Diphosphate Ribose, Protein Binding, Protein Structure, Secondary, Sequence Deletion, Structure-Activity Relationship

Journal Title

J Biol Chem

Conference Name

Journal ISSN

0021-9258
1083-351X

Volume Title

Publisher

Elsevier BV
Sponsorship
Cancer Research UK (18796)
Cancer Research Uk (None)
This work was funded by Fellowships and Project Grants (to JPM and DPR) from the National Health and Medical Research Council of Australia.