The N-terminal region of CHD4 is essential for activity and contains a HMG-box-like-domain that can bind poly(ADP-ribose)
Silva, Ana PG
Ryan, Daniel P
Low, Jason KK
Mackay, Joel P
The Journal of Biological Chemistry
The American Society for Biochemistry and Molecular Biology
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Silva, A. P., Ryan, D. P., Galanty, Y., Low, J. K., Vandevenne, M., Jackson, S., & Mackay, J. P. (2015). The N-terminal region of CHD4 is essential for activity and contains a HMG-box-like-domain that can bind poly(ADP-ribose). The Journal of Biological Chemistry https://doi.org/10.1074/jbc.M115.683227
Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNAdamage 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 Nterminal region. The fold consists of a four α-helix bundle with structural similarity to the High Mobility Group (HMG) 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.
CHD4, NuRD, DNA damage, HMG-box, DNA binding protein, poly(ADP-ribose), nucleosome, chromatin remodeling
This work was funded by Fellowships and Project Grants (to JPM and DPR) from the National Health and Medical Research Council of Australia.
Cancer Research UK (A18796)
External DOI: https://doi.org/10.1074/jbc.M115.683227
This record's URL: https://www.repository.cam.ac.uk/handle/1810/254676