The DOI matches its Crossref record; 45 of the 47 references it cites were found in a registry or an index.
SIRT6 Recruits SNF2H to DNA Break Sites, Preventing Genomic Instability through Chromatin Remodeling
Open accessAbstract
DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.
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“The recruitment of SIRT6 to sites of DNA damage helps to remodel the local chromatin environment through deacetylation of H3K56 and allow DNA repair machinery to access the DNA (Toiber et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Toiber et al., 2013
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Cites
1 retracted
RETRACTED: Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation
Kaidi, A., Weinert, B. T., Choudhary, C., & Jackson, S. P. (2010) · Science · doi:10.1126/science.1192049 · Cited by 366
RetractedThe DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368
Playing the End Game: DNA Double-Strand Break Repair Pathway Choice
Chapman, J. R., Taylor, M. R. G., & Boulton, S. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.07.029 · Cited by 1,728
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Bunting, S. F., Callén, E., Wong, N., Chen, H.-T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010) · Cell · doi:10.1016/j.cell.2010.03.012 · Cited by 1,671
Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6
Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., et al. (2006) · Cell · doi:10.1016/j.cell.2005.11.044 · Cited by 1,637
Self-citationRecent progress in the biology and physiology of sirtuins
Finkel, T., Deng, C., & Mostoslavsky, R. (2009) · Nature · doi:10.1038/nature08197 · Cited by 1,506
Self-citationThe sirtuin SIRT6 regulates lifespan in male mice
Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., Bar-Joseph, Z., & Cohen, H. Y. (2012) · Nature · doi:10.1038/nature10815 · Cited by 1,059
The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α
Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R. E., Vadysirisack, D. D., Guimaraes, A., Marinelli, B., Wikstrom, J. D., Nir, T., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.041 · Cited by 1,001
Self-citationSIRT6 Promotes DNA Repair Under Stress by Activating PARP1
Mao, Z., Hine, C., Tian, X., Van Meter, M., Au, M., Vaidya, A., Seluanov, A., & Gorbunova, V. (2011) · Science · doi:10.1126/science.1202723 · Cited by 867
CBP/p300-mediated acetylation of histone H3 on lysine 56
Das, C., Lucia, M. S., Hansen, K. C., & Tyler, J. K. (2009) · Nature · doi:10.1038/nature07861 · Cited by 698
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Li, Y., & Seto, E. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026831 · Cited by 1,337
DNA damage and its links to neurodegeneration
Madabhushi, R., Pan, L., & Tsai, L.-H. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.034 · Cited by 654
Epigenetic regulation of ageing: linking environmental inputs to genomic stability
Benayoun, B. A., Pollina, E. A., & Brunet, A. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4048 · Cited by 610
Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes
Etchegaray, J., & Mostoslavsky, R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.029 · Cited by 546
Self-citationBooth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499
Metadata
- Authors
- Toiber, D., Erdel, F., Bouazoune, K., Silberman, D. M., Zhong, L., Mulligan, P., Sebastian, C., Cosentino, C., Martinez-Pastor, B., Giacosa, S., D’Urso, A., Näär, A. M., Kingston, R., Rippe, K., & Mostoslavsky, R.
- Affiliations
- Harvard University (US)
- German Cancer Research Center (DE)
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 51
- Issue
- 4
- Pages
- 454-468
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3761390
- OpenAlex
- W2055373932
- Cited by
- 381
- References
- 47
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 19 · 2023: 28 · 2022: 27 · 2021: 35 · 2020: 38 · 2019: 33 · 2018: 28 · 2017: 25 · 2016: 45 · 2015: 25 · 2014: 30 · 2013: 5
- FWCI
- 15.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-nd)
- Funders
- Ellison Medical Foundation
- Fondazione Umberto Veronesi
- National Institutes of Health
- National Institute of General Medical Sciences (GM093072-01, R01GM093072)
- Congressionally Directed Medical Research Programs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- SIRT6, SNF2H, chromatin remodeling, DNA double-strand breaks, DNA damage response, genomic instability, 53BP1, BRCA1, histone deacetylase, chromatin accessibility, DNA repair
- MeSH terms
- Adenosine Triphosphatases, Animals, Cells, Cultured, Cerebral Cortex, Chromatin, Chromosomal Proteins, Non-Histone, DNA Damage, DNA Repair, Hippocampus, Histones, Humans, Nucleosomes, Mice, Knockout, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Sirtuins, Chromatin Assembly and Disassembly, Genomic Instability, Chromatin Immunoprecipitation, Immunoprecipitation, Mice
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