Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.
The SGS1 gene of yeast encodes a DNA helicase with homology to the human WRN gene. Mutations in WRN result in Werner's syndrome, a disease with symptoms resembling premature aging. Mutation of SGS1 is shown to cause premature aging in yeast mother cells on the basis of a shortened life-span and the aging-induced phenotypes of sterility and redistribution of the Sir3 silencing protein from telomeres to the nucleolus. Further, in old sgs1 cells the nucleolus is enlarged and fragmented-changes that also occur in old wild-type cells. These findings suggest a conserved mechanism of cellular aging that may be related to nucleolar structure.
Sinclair
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Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mills
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Guarente
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D002455:Cell Division; D002466:Cell Nucleolus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D016922:Cellular Senescence; D004265:DNA Helicases / Q000235:genetics* / Q000502:physiology; D005090:Exodeoxyribonucleases; D019084:Fluorescent Antibody Technique, Indirect; D005656:Fungal Proteins / Q000032:analysis; D005800:Genes, Fungal; D006801:Humans; D009154:Mutation; D010641:Phenotype; D053484:RecQ Helicases; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators / Q000032:analysis; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase
D005656:Fungal Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; D005090:Exodeoxyribonucleases; C090472:SGS1 protein, S cerevisiae; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase