Cited by 2,253Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceSirtuins and Resveratrol in Medicine

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

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Kaeberlein, M., McVey, M., Guarente, L.·1999·Genes & Development

Abstract

The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed.

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Crossref · 10.1101/gad.13.19.2570

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  • Loss of Sir2 increases rDNA recombination and shortens life span.

    “Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”

    From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Kaeberlein et al., 1999

  • An extra genomic copy of Sir2 increases rDNA stability and extends life span.

    “Loss of Sir2 increases rDNA recombination and shortens life span; whereas an extra genomic copy of Sir2, which increases rDNA stability, extends life span (Kaeberlein et al., 1999”

    From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as Kaeberlein et al., 1999

  • Increasing Sir2 level in yeast increases lifespan.

    “Furthermore, increasing the level of Sir2 in yeast increases lifespan (Kaeberlein et al., 1999).”

    From The Aging Epigenome (2016) · cites this paper as Kaeberlein et al., 1999

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Authors
Kaeberlein, M., McVey, M., & Guarente, L.
Affiliations
Massachusetts Institute of Technology (US)
Venue
Genes & Development
Published
1999-10-01
Volume
13
Issue
19
Pages
2570-2580
ISSN
0890-9369 (ISSN-L)
OpenAlex
W2157649587
Cited by
2,253
References
52
Citations by year
2026: 27 · 2025: 64 · 2024: 50 · 2023: 80 · 2022: 76 · 2021: 91 · 2020: 93 · 2019: 101 · 2018: 126 · 2017: 73 · 2016: 123 · 2015: 104 · 2014: 111 · 2013: 127 · 2012: 123
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM07287, T32GM007287)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
Sir2p, Sir3p, longevity, lifespan regulation, Saccharomyces cerevisiae, non-homologous end joining, replication block, gene dosage, aging
MeSH terms
Mating Factor, DNA-Binding Proteins, DNA, Fungal, DNA, Ribosomal, Fungal Proteins, Histone Deacetylases, Peptides, Phenotype, Saccharomyces cerevisiae, Trans-Activators, Mutagenesis, Saccharomyces cerevisiae Proteins, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2

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