title: Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Kennedy
authors.forename: M
authors.initials: M
authors.lastname: Gotta
authors.forename: D A
authors.initials: DA
authors.lastname: Sinclair
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: D S
authors.initials: DS
authors.lastname: McNabb
authors.forename: M
authors.initials: M
authors.lastname: Murthy
authors.forename: S M
authors.initials: SM
authors.lastname: Pak
authors.forename: T
authors.initials: T
authors.lastname: Laroche
authors.forename: S M
authors.initials: SM
authors.lastname: Gasser
authors.forename: L
authors.initials: L
authors.lastname: Guarente
mesh_terms: D018797:Cell Cycle Proteins; D002466:Cell Nucleolus / Q000737:chemistry / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D005800:Genes, Fungal / Q000502:physiology; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C449502:MPT5 protein, S cerevisiae; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C084122:SIR3 protein, S cerevisiae; C061573:SIR4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators