A phylogenetically conserved NAD + -dependent protein deacetylase activity in the Sir2 protein family
Open accessAbstract
The yeast Sir2 protein, required for transcriptional silencing, has an NAD + -dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD + -dependent HDA activity that is eliminated in a yeast strain from which SIR2 and its four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial, and human proteins, and depends completely on NAD + in all species tested. The yeast NPT1 gene, encoding an important NAD + synthesis enzyme, is required for rDNA and telomeric silencing and contributes to silencing of the HM loci. Null mutants in this gene have significantly reduced intracellular NAD + concentrations and have phenotypes similar to sir2 null mutants. Surprisingly, yeast from which all five SIR2 homologs have been deleted have relatively normal bulk histone acetylation levels. The evolutionary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evolutionarily conserved signal transduction pathway that monitors cellular energy and redox states.
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In Saccharomyces cerevisiae, the longevity protein Sir2 exhibited its lifespan-promoting effects in an NAD+-dependent manner.
“However, another key discovery was made more recently in Saccharomyces cerevisiae, showing that the longevity protein Sir2 (the yeast sirtuin) exhibited its lifespan-promoting effects in an NAD+-dependent manner12,73,74.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [74]
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- Authors
- Smith, J. S., Brachmann, C. B., Celic, I., Kenna, M. A., Muhammad, S., Starai, V. J., Avalos, J. L., Escalante-Semerena, J. C., Grubmeyer, C., Wolberger, C., & Boeke, J. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Department of Molecular Biology and Genetics, Department of Biophysics and Biophysical Chemistry, and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Bacteriology, University of Wisconsin, Madison, WI 53706; and School of Medicine, Temple University, Philadelphia, PA 19140
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-06-06
- Volume
- 97
- Issue
- 12
- Pages
- 6658-6663
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18692
- OpenAlex
- W2017525855
- Cited by
- 718
- References
- 42
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 14 · 2023: 16 · 2022: 12 · 2021: 18 · 2020: 23 · 2019: 19 · 2018: 20 · 2017: 22 · 2016: 21 · 2015: 27 · 2014: 24 · 2013: 31 · 2012: 28
- FWCI
- 30.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9724924)
- National Institutes of Health
- National Cancer Institute (CA-16519, P01CA016519)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- NAD+-dependent histone deacetylase, histone deacetylation, transcriptional silencing, Sir2p, NAD biosynthesis, telomeric silencing, rDNA silencing, histone acetylation, evolutionary conservation
- MeSH terms
- DNA, Ribosomal, Fungal Proteins, Histone Deacetylases, Histones, NAD, Phylogeny, Poly(ADP-ribose) Polymerases, Recombination, Genetic, Saccharomyces cerevisiae, Trans-Activators, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 1, Sirtuin 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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