Inactivation of yeast Isw2 chromatin remodeling enzyme mimics longevity effect of calorie restriction via induction of genotoxic stress response
Open accessAbstract
ATP-dependent chromatin remodeling is involved in all DNA transactions and is linked to numerous human diseases. We explored functions of chromatin remodelers during cellular aging. Deletion of ISW2, or mutations inactivating the Isw2 enzyme complex, extends yeast replicative lifespan. This extension by ISW2 deletion is epistatic to the longevity effect of calorie restriction (CR), and this mechanism is distinct from suppression of TOR signaling by CR. Transcriptome analysis indicates that isw2Δ partially mimics an upregulated stress response in CR cells. In particular, isw2Δ cells show an increased response to genotoxic stresses, and the DNA repair enzyme Rad51 is important for isw2Δ-mediated longevity. We show that lifespan is also extended in C. elegans by reducing levels of athp-2, a putative ortholog of Itc1/ACF1, a critical subunit of the enzyme complex. Our findings demonstrate that the ISWI class of ATP-dependent chromatin remodeling complexes plays a conserved role during aging and in CR.
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Caloric restriction in yeast involves nucleosome remodeling.
“caloric restriction in yeast involves nucleosome remodeling (Dang et al., 2014).”
From The Aging Epigenome (2016) · cites this paper as Dang et al., 2014
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- Authors
- Dang, W., Sutphin, G. L., Dorsey, J. A., Otte, G. L., Cao, K., Perry, R. M., Wanat, J. J., Saviolaki, D., Murakami, C. J., Tsuchiyama, S., Robison, B., Gregory, B. D., Vermeulen, M., Shiekhattar, R., Johnson, F. B., Kennedy, B. K., Kaeberlein, M., & Berger, S. L.
- Affiliations
- University of Pennsylvania (US)
- University of Washington (US)
- The Wistar Institute (US)
- Buck Institute for Research on Aging (US)
- University Medical Center Utrecht (NL)
- Corresponding author
- Berger, Shelley L.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 19
- Issue
- 6
- Pages
- 952-966
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4106248
- OpenAlex
- W1967875119
- Cited by
- 83
- References
- 67
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 10 · 2016: 10 · 2015: 8
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Institute on Aging (P01AG031862, R01AG043080, T32AG000057, R01AG039390, R00AG037646, K99AG037646)
- National Cancer Institute (P30CA010815)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- ISW2, ATP-dependent chromatin remodeling, replicative lifespan, cellular aging, caloric restriction, longevity, genotoxic stress response, DNA repair, RAD51, TOR signaling, epistasis, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, Animals, DNA Damage, DNA Repair, Longevity, Peroxidases, Saccharomyces cerevisiae, Stress, Physiological, Transcription Factors, Gene Expression Regulation, Fungal, Cellular Senescence, Caenorhabditis elegans, Gene Expression Profiling, Saccharomyces cerevisiae Proteins, Caenorhabditis elegans Proteins, Caloric Restriction, Chromatin Assembly and Disassembly, Rad51 Recombinase, Gene Knockout Techniques
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