Cited by 718Sirtuins and Resveratrol in MedicineNuclear Structure and FunctionGenomics and Chromatin Dynamics

A phylogenetically conserved NAD + -dependent protein deacetylase activity in the Sir2 protein family

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Smith, Jeffrey S., Brachmann, Carrie Baker, Celic, Ivana, Kenna, Margaret A., Muhammad, Shabazz, Starai, Vincent J., Avalos, Jose L., Escalante-Semerena, Jorge C. +3 more·2000·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.97.12.6658

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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.”

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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
Published
2000-06-06
Volume
97
Issue
12
Pages
6658-6663
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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

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