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

  1. Matt Kaeberlein,
  2. Mitch McVey, and
  3. Leonard Guarente
  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA

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 α 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.

Keywords

Footnotes

  • These authors contributed equally to this work.

  • Corresponding author.

  • E-MAIL leng{at}mit.edu; FAX (617) 253–8699.

    • Received June 21, 1999.
    • Accepted August 12, 1999.
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