Authors: Kennedy BK; Gotta M; Sinclair DA; Mills K; McNabb DS; Murthy M; Pak SM; Laroche T; Gasser SM; Guarente L
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.
Keywords: Cell Aging/physiology; *Cell Cycle Proteins; Cell Nucleolus/chemistry/*metabolism; Fungal Proteins/*genetics/*metabolism; Gene Expression Regulation, Fungal/physiology; Genes, Fungal/physiology; Molecular Sequence Data; Mutagenesis/physiology; RNA-Binding Proteins; *Repressor Proteins; Saccharomyces cerevisiae/chemistry/*cytology/ultrastructure; *Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; *Silent Information Regulator Proteins, Saccharomyces cerevisiae; Telomere/chemistry/*metabolism; Trans-Activators/metabolism
Journal: Cell Volume: 89 Issue: 3 Pages: 381-91 Date: May 2, 1997 PMID: 9150138 |
Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L (1997) Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell 89: 381-91.
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