Redistribution of Silencing Proteins from Telomeres to the Nucleolus Is Associated with Extension of Life Span in S. cerevisiae

• Published in: Cell 1997-05, Vol.89 (3), p.381-391
• Main Authors: Kennedy, Brian K, Gotta, Monica, Sinclair, David A, Mills, Kevin, McNabb, David S, Murthy, Mala, Pak, Sally M, Laroche, Thierry, Gasser, Susan M, Guarente, Leonard
• Format: Article
• Language: English
• Subjects: 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; Repressor Proteins; RNA-Binding Proteins; Saccharomyces cerevisiae; 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
• ISSN: 0092-8674; 1097-4172
• 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.