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)
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)
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.
- Australian National University Australia
- University of Sydney Australia
- University of Cambridge United Kingdom
Models, Molecular, HMG-box, Poly Adenosine Diphosphate Ribose, Molecular Sequence Data, 612, Autoantigens, Protein Structure, Secondary, chromatin remodeling, Structure-Activity Relationship, nucleosome remodeling deacetylase (NuRD), Humans, DNA Breaks, Double-Stranded, Amino Acid Sequence, Conserved Sequence, Sequence Deletion, poly(ADP-ribose), nucleosome, DNA, Chromatin Assembly and Disassembly, DNA binding protein, CHD4, Nucleosomes, HEK293 Cells, HMG-Box Domains, DNA damage, Peptides, DNA Damage, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Protein Binding
Models, Molecular, HMG-box, Poly Adenosine Diphosphate Ribose, Molecular Sequence Data, 612, Autoantigens, Protein Structure, Secondary, chromatin remodeling, Structure-Activity Relationship, nucleosome remodeling deacetylase (NuRD), Humans, DNA Breaks, Double-Stranded, Amino Acid Sequence, Conserved Sequence, Sequence Deletion, poly(ADP-ribose), nucleosome, DNA, Chromatin Assembly and Disassembly, DNA binding protein, CHD4, Nucleosomes, HEK293 Cells, HMG-Box Domains, DNA damage, Peptides, DNA Damage, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Protein Binding
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