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PMID:10521401
| Citation |
Kaeberlein, M, McVey, M and Guarente, L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 13:2570-80 |
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| Abstract |
The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed. |
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| Keywords |
DNA, Fungal; DNA, Ribosomal; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Fungal Proteins/genetics; Fungal Proteins/physiology; Histone Deacetylases; Mutagenesis; Peptides; Phenotype; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/physiology; Saccharomyces cerevisiae Proteins; Silent Information Regulator Proteins, Saccharomyces cerevisiae; Sirtuin 2; Sirtuins; Trans-Activators/genetics; Trans-Activators/physiology |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0090344 : negative regulation of cell aging |
ECO:0000315: |
P |
Fig.1(A)shows that sir2 the mutant strain demonstrated a severe reduction in mean life span(approx.50%). Fig.7(A)Overexpression of SIR2 extends the life span of W303R by approx.30%. |
complete | ||||
| GO:0007569 : cell aging |
ECO:0000315: |
P |
Fig.1(A)demonstrates disruption of sir3 resulted in a 20% decrease in mean life span. |
complete | ||||
| GO:0007569: cell aging |
ECO:0000315: |
P |
Fig.1(A)demonstrates that disruption of sir4 resulted in a 20 % decrease in mean life span. |
complete | ||||
| GO:0007580 : extrachromosomal circular DNA accumulation involved in cell aging |
ECO:0000315: |
P |
Figure 4.Accumulation of ERCs occurs more rapidly in a sir2 mutant than in wild-type mother cells when the cell is FOB1 dependent.Mutation of fob1 in sir2D hmlD mother cells decreases ERC accumulation below levels observed in wild-type cells. |
complete | ||||
| GO:0007569 : cell aging |
ECO:0000315: |
P |
Figure 6.shows that Mutation of fob1 suppresses the life span defect of a sir2 mutant. |
complete | ||||
See also
References
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