Cited by 374DNA Repair MechanismsChromatin Remodeling and CancerGenomics and Chromatin Dynamics

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Regulation of DNA‐damage responses and cell‐cycle progression by the chromatin remodelling factor CHD4

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Polo, Sophie E, Kaidi, Abderrahmane, Baskcomb, Linda, Galanty, Yaron, Jackson, Stephen P·2010·The EMBO Journal

DOI 10.1038/emboj.2010.188PMC PMC2944064

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Abstract

The chromatin remodelling factor chromodomain helicase DNA‐binding protein 4 (CHD4) is a catalytic subunit of the NuRD transcriptional repressor complex. Here, we reveal novel functions for CHD4 in the DNA‐damage response (DDR) and cell‐cycle control. We show that CHD4 mediates rapid poly(ADP‐ribose)‐dependent recruitment of the NuRD complex to DNA‐damage sites, and we identify CHD4 as a phosphorylation target for the apical DDR kinase ataxia‐telangiectasia mutated. Functionally, we show that CHD4 promotes repair of DNA double‐strand breaks and cell survival after DNA damage. In addition, we show that CHD4 acts as an important regulator of the G1/S cell‐cycle transition by controlling p53 deacetylation. These results provide new insights into how the chromatin remodelling complex NuRD contributes to maintaining genome stability. This paper adds to the emerging concept that chromatin remodelling contributes to DNA‐damage responses. CHD4, a known NuRD component, is identified as ATM target, localizes to DNA breaks and contributes to repair while associating with PARPylated factors.

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Additional file 2 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127596
Additional file 7 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767919
Additional file 1 of The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
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Additional file 3 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767907
Additional file 1 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127584
Additional file 5 of The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Wang, J., Zhong, F., Li, J., Yue, H., Li, W., & Lü, X. (2023) · Figshare · doi:10.6084/m9.figshare.22598672
Additional file 5 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127608
Additional file 4 of The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Wang, J., Zhong, F., Li, J., Yue, H., Li, W., & Lü, X. (2023) · Figshare · doi:10.6084/m9.figshare.22598669
Additional file 4 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767910
Additional file 5 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767913
Additional file 7 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127617
Additional file 3 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127602
Additional file 4 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127605
Additional file 3 of The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Wang, J., Zhong, F., Li, J., Yue, H., Li, W., & Lü, X. (2023) · Figshare · doi:10.6084/m9.figshare.22598666
Additional file 2 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767904
Additional file 6 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767916
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Additional file 6 of CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Xu, N., Liu, F., Wu, S., Ye, M., Ge, H., Zhang, M., Song, Y., Tong, L., Zhou, J., & Bai, C. (2020) · Figshare · doi:10.6084/m9.figshare.12127614
Additional file 11 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767895
Additional file 1 of Mouse Chd4-NURD is required for neonatal spermatogonia survival and normal gonad development
de Castro, R. O., Carbajal, A., de Almeida, L. P., Goitea, V. E., Griffin, C. T., & Pezza, R. J. (2022) · Figshare · doi:10.6084/m9.figshare.19767901
Additional file 2 of The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Wang, J., Zhong, F., Li, J., Yue, H., Li, W., & Lü, X. (2023) · Figshare · doi:10.6084/m9.figshare.22598663
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Zhang, M., Liu, D., Liu, G., Zhu, M., & Pan, F. (2026) · Andrology · doi:10.1111/andr.70232
“…41, 72, 73 ] DNA damage repair CHD4 mediates DSB repair via homologous recombination, CHD7 facilitates the assembly of the NHEJ repair pathway [ 77, 79, 82, 85 ] Abbreviations: GDNF, glial cell line-derived neurotrophic factor; NuRD, nucleosome remodeling and deacetylase; SALL4, Sal-like 4.…”
CHD4 Orchestrates Chromatin Remodeling to Activate the c‐Myc Signaling Pathway in Cancer Pathogenesis
Ding, P., Cao, Y., Liu, Z., Xie, J., Liu, L., Sun, S., Yu, X., Deng, Z., Fan, Z., Yang, Y. F., et al. (2026) · MedComm – Oncology · doi:10.1002/mog2.70073
Mi-2 and E93 coordinate robust cell cycle exit with terminal differentiation through enhancer decommissioningPreprint
Buchert, E. M., Fogarty, E. A., Ma, Y., Mehta, S. J. K., McKay, D. J., & Buttitta, L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.16.752104
Mechanism of ATP Hydrolysis and Regulation Behind Chromatin Remodeling
Zhao, Y., & Hong, J. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1016397
Variation, modification, and reorganization of broken chromatin
Humphrey, T. C., Downs, J. A., & Chambers, A. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00014-3
Regulation of chromatin structure and function by adenosine diphosphate (ADP)-ribosylation
Huang, D., Edwards, A. D., & Kraus, W. L. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00007-6
Circ_0024390 promotes renal tubular EMT through the miR-6890-3p/CHD4 axis: implications for renal interstitial fibrosis
Yang, X., Zhang, L., Song, Y., & Liu, G. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1941987
“…has been implicated in multiple pathological processes, including cell cycle dysregulation, hypoxia-related signaling pathways, excessive glycolysis, EMT, and the maintenance of tumor cell stemness (Coassolo et al., 2021; Fu et al., 2011; Zhang et al., 2022; Polo et al., 2010; Wang et al., 2020).”
Investigating Tumor Suppressors in the DNA Damage Response: Caretakers of the Genome and Biomarkers to Predict Therapeutic Response: A Dissertation
Guillemette, S. (2014) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2w59b
“In fulfillment of the requirements for the degree of”
Background

Authors: Polo, S. E., Kaidi, A., Baskcomb, L., Galanty, Y., & Jackson, S. P.
Affiliations: University of Cambridge (GB)
Corresponding author: Jackson, Stephen P
ORCID: Polo, Sophie E
Kaidi, Abderrahmane
Galanty, Yaron
Jackson, Stephen P
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2010-08-06
Volume: 29
Issue: 18
Pages: 3130-3139
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/emboj.2010.188
PMC: PMC2944064
OpenAlex: W2020084014
Cited by: 374
References: 56
Citations by year: 2026: 13 · 2025: 14 · 2024: 20 · 2023: 17 · 2022: 26 · 2021: 17 · 2020: 22 · 2019: 18 · 2018: 18 · 2017: 35 · 2016: 24 · 2015: 17 · 2014: 31 · 2013: 34 · 2012: 31
FWCI: 13.30
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/3.0/ (tdm)
creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
Locations: The EMBO Journal (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Explore Bristol Research (submittedVersion)
Funders: Wellcome Trust
Cancer Research UK (11224, A5290, A4361)
European Commission (512113, 201630, LSHG-CT-2005-512113)
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: CHD4, chromatin remodeling, NuRD complex, DNA damage response, cell cycle regulation, G1/S transition, p53 deacetylation, ATM phosphorylation, DNA double-strand break repair, poly(ADP-ribose), poly(ADP-ribose) polymerase, genome stability, transcriptional repressor
MeSH terms: Animals, Autoantigens, Cell Cycle, DNA Damage, DNA Helicases, DNA-Binding Proteins, Fluorescent Antibody Technique, Histones, Humans, Phosphorylation, Poly Adenosine Diphosphate Ribose, RNA, Messenger, Blotting, Western, Tumor Suppressor Protein p53, Protein Serine-Threonine Kinases, Mice, Knockout, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Chromatin Assembly and Disassembly, Immunoprecipitation, Mice, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Ataxia Telangiectasia Mutated Proteins

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Regulation of DNA‐damage responses and cell‐cycle progression by the chromatin remodelling factor CHD4

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