Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.
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.
Kennedy
B K
BK
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Gotta
M
M
Sinclair
D A
DA
Mills
K
K
McNabb
D S
DS
Murthy
M
M
Pak
S M
SM
Laroche
T
T
Gasser
S M
SM
Guarente
L
L
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
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