The NuRD chromatin–remodeling complex regulates signaling and repair of DNA damage
Open accessAbstract
Cells respond to ionizing radiation (IR)–induced DNA double-strand breaks (DSBs) by orchestrating events that coordinate cell cycle progression and DNA repair. How cells signal and repair DSBs is not yet fully understood. A genome-wide RNA interference screen in Caenorhabditis elegans identified egr-1 as a factor that protects worm cells against IR. The human homologue of egr-1, MTA2 (metastasis-associated protein 2), is a subunit of the nucleosome-remodeling and histone deacetylation (NuRD) chromatin-remodeling complex. We show that knockdown of MTA2 and CHD4 (chromodomain helicase DNA-binding protein 4), the catalytic subunit (adenosine triphosphatase [ATPase]) of NuRD, leads to accumulation of spontaneous DNA damage and increased IR sensitivity. MTA2 and CHD4 accumulate in DSB-containing chromatin tracks generated by laser microirradiation. Directly at DSBs, CHD4 stimulates RNF8/RNF168-dependent formation of ubiquitin conjugates to facilitate the accrual of RNF168 and BRCA1. Finally, we show that CHD4 promotes DSB repair and checkpoint activation in response to IR. Thus, the NuRD chromatin–remodeling complex is a novel regulator of DNA damage responses that orchestrates proper signaling and repair of DSBs.
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Other repressive complexes, such as NuRD and histone deacetylases (HDACs), also transiently accumulate at DSBs.
“Other repressive complexes, such as NuRD and histone deacetylases (HDACs) (43)(44)(45)(46), also transiently accumulate at DSBs, supporting this idea.”
From DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin (2014) · cites this paper as [45]
The Results and discussion section, “NuRD rapidly accumulates within DSB-flanking chromatin” (page unavailable), reports that NuRD subunits accumulate at DSB tracks within seconds. The paper does not establish that this accumulation is transient: it reports steady-state levels at three minutes. It also does not show that HDACs, as a separate group, accumulate at DSBs. (LLM, conf=0.83)
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References 47 · Cited by 243
- Authors
- Smeenk, G., Wiegant, W. W., Vrolijk, H., Solari, A. P., Pastink, A., & van Attikum, H.
- Affiliations
- Leiden University Medical Center (NL)
- Department of Toxicogenetics 1 , 2 , and 3
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-08-30
- Volume
- 190
- Issue
- 5
- Pages
- 741-749
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2935570
- OpenAlex
- W2162951729
- Cited by
- 243
- References
- 47
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 7 · 2021: 6 · 2020: 15 · 2019: 11 · 2018: 12 · 2017: 16 · 2016: 19 · 2015: 17 · 2014: 20 · 2013: 25 · 2012: 23
- FWCI
- 10.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- 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
- NuRD complex, MTA2, CHD4, DNA double-strand breaks, radiosensitivity, DNA damage response, DNA repair, BRCA1, DNA damage checkpoint, chromatin remodeling, EGR1, Caenorhabditis elegans
- MeSH terms
- Adenosine Triphosphatases, Cell Survival, Chromatin, Chromosomes, DNA Damage, DNA Repair, Histones, Humans, Nucleosomes, Transfection, Signal Transduction, Comet Assay, Ubiquitin, RNA Interference, RNA, Small Interfering, Chromatin Assembly and Disassembly, Cell Line, Tumor, DNA Breaks, Double-Stranded
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