Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae

Cell. 1997 May 2;89(3):381-91. doi: 10.1016/s0092-8674(00)80219-6.


A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle Proteins*
  • Cell Nucleolus / chemistry
  • Cell Nucleolus / metabolism*
  • Cellular Senescence / physiology
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal / physiology
  • Genes, Fungal / physiology
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • RNA-Binding Proteins
  • Repressor Proteins*
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Telomere / chemistry
  • Telomere / metabolism*
  • Trans-Activators / metabolism


  • Cell Cycle Proteins
  • Fungal Proteins
  • MPT5 protein, S cerevisiae
  • RNA-Binding Proteins
  • Repressor Proteins
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators