OrganismSaccharomyces cerevisiae (replicative)
Aging PhenotypeShortened life-span
Allele TypeDeletion
DescriptionDeletion of SIR4 results in a 20-25% reduction in life-span (Kaeberlein et al., 1999). This reduction in life-span is suppressed by preventing mating type heterozygosity (co-expression of MATa and MATalpha).
Gene Functionsilencing factor
Other PhenotypesThe sir4-42 allele confers extended life-span in a strain carrying a C-terminal truncation of MPT5/UTH4 (Kennedy et al., 1995)
Both Sir3p and Sir4p relocate to the nucleolus in the sir4-42 mutant background, dependent upon MPT5 and YGL023 (Kennedy et al., 1997)
SIR4 deletion mutants show loss of silencing at the silent mating type loci (Rine and Herskowitz, 1987) and telomeres (Aparicio et al., 1991) and have a slightly elevated level of rDNA marker loss (Kaeberlein et al., 1999).
HomologsS.c. YDR485, SPC105, CNM67
S.p. Spbc1639.02c, Spcc825.01
C.e. unc-89, Y55B1BR3
D.m. CG10562
M.m. Acz
H.s. P130
Primary ReferenceKaeberlein, 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. [Abstract]
Other ReferencesAparicio, O. M., Billington, B. L., and Gottschling, D. E. (1991). Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. Cell 66, 1279-87. [Abstract]
Kennedy, B. K., Austriaco, N. R., Zhang, J., and Guarente, L. (1995). Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80, 485-96. [Abstract]
Kennedy, B. K., Gotta, M., Sinclair, D. A., Mills, K., McNabb, D. S., Murthy, M., Pak, S. M., Laroche, T., Gasser, S. M., and Guarente, L. (1997). Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life sp [Abstract]
Rine, J., and Herskowitz, I. (1987). Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics 116, 9-22. [Abstract]
Relevant LinksSGD:
KeywordsDNA damage, silencing, chromatin, telomeres, rDNA, yeast, replicative senescence, Saccharomyces, cerevisiae, sterility, starvation resistance