ArticleNucleic acids research2020
SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.Nucleic acids research · 2026Review
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Role of CHD4 in tumor progression, DNA damage response and treatment resistance (Review).Oncology reports · 2026Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Chromatin Remodeling, DNA Double-Strand Break Repair, and Human Disease: How a Breakup Changes You.Biomolecules · 2026Review
- Targeting the Golgi apparatus enhances PD-L1 blockade and synergizes with oxaliplatin to improve immunotherapy efficacy.The Journal of biological chemistry · 2026Article
- CHD4 epigenetically coordinates genomic instability and immunosuppression to drive pan-cancer progression and confer HDAC inhibitor sensitivity.Clinical and experimental medicine · 2026Article
- The NuRD chromatin remodeling complex contributes to repairing exogenous double-strand breaks in the Caenorhabditis elegans germline.Genetics · 2026Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- GPR40 activation alleviates pulmonary fibrosis by repressing M2 macrophage polarization through the PKD1/CD36/TGF-β1 pathway.Acta pharmacologica Sinica · 2025Article
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- NuRD chromatin remodeling is required to repair exogenous DSBs in thebioRxiv : the preprint server for biology · 2025Article
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia.The Journal of experimental medicine · 2025Article
- hnRNPA2B1 deacetylation by SIRT6 restrains local transcription and safeguards genome stability.Cell death and differentiation · 2025Article
- Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.Nature reviews. Molecular cell biology · 2024Review
- The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.Biomedicines · 2024Review
- Deep learning with a small dataset predicts chromatin remodelling contribution to winter dormancy of apple axillary buds.Tree physiology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic instability is an underlying hallmark of cancer and is closely associated with defects in DNA damage repair (DDR). Chromatin relaxation is a prerequisite for DDR, but how chromatin accessibility is regulated remains elusive. Here we report that the histone deacetylase SIRT6 coordinates with the chromatin remodeler CHD4 to promote chromatin relaxation in response to DNA damage. Upon DNA damage, SIRT6 rapidly translocates to DNA damage sites, where it interacts with and recruits CHD4. Once at the damage sites, CHD4 displaces heterochromatin protein 1 (HP1) from histone H3 lysine 9 trimethylation (H3K9me3). Notably, loss of SIRT6 or CHD4 leads to impaired chromatin relaxation and disrupted DNA repair protein recruitment. These molecular changes, in-turn, lead to defective homologous recombination (HR) and cancer cell hypersensitivity to DNA damaging agents. Furthermore, we show that SIRT6-mediated CHD4 recruitment has a specific role in DDR within compacted chromatin by HR in G2 phase, which is an ataxia telangiectasia mutated (ATM)-dependent process. Taken together, our results identify a novel function for SIRT6 in recruiting CHD4 onto DNA double-strand breaks. This newly identified novel molecular mechanism involves CHD4-dependent chromatin relaxation and competitive release of HP1 from H3K9me3 within the damaged chromatin, which are both essential for accurate HR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.