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

Brian K. Kennedy, Monica Gotta, David A. Sinclair, Kevin Mills, David S. McNabb, Mala Murthy, Sally M. Pak, Thierry Laroche, Susan M. Gasser, Leonard Guarente

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)381-391
Number of pages11
JournalCell
Volume89
Issue number3
DOIs
StatePublished - May 2 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kennedy, B. K., Gotta, M., Sinclair, D. A., Mills, K., McNabb, D. S., Murthy, M., Pak, S. M., Laroche, T., Gasser, S. M., & Guarente, L. (1997). Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell, 89(3), 381-391. https://doi.org/10.1016/S0092-8674(00)80219-6