NameSIR2
OrganismSaccharomyces cerevisiae (replicative)
Aging PhenotypeLife-span extension
Allele TypeOverexpression
StrainW303R
DescriptionSingle copy overexpression of SIR2 extends life-span by approximately 35% in W303R (Kaeberlein et al., 1999). Deletion shortens life-span by approximately 50% (Kaeberlein et al., 1999). The short life-span is likely caused by an increased rate of formation of extrachromosomal rDNA circles (Kaeberlein et al., 1999).
Gene FunctionNAD-dependent histone deacetylase. (Imai et al., 2000).
ADP-ribosyltransferase (Tanny et al., 1999).
Other PhenotypesSIR2 is required for life-span extension by calorie restriction (Lin et al., 2000), high osmolarity (Kaeberlein et al., 2002), and HAP4-overexpression (Lin et al., 2002).
Overexpression of a C. elegans homolog, Sir-2.1, extends life-span in that organism (Tissenbaum and Guarente, 2001).
SIR2 mutants are defective for telomere (Aparicio et al., 1991) and HM silencing (Shore et al., 1984; Rine and Herskowitz, 1987). Mutation of SIR2 also causes increased rDNA recombination (Gottlieb and Esposito, 1989) and results in a loss of rDNA silencing (Bryk et al., 1997, Smith et al., 1997).
HomologsS.c. HST1, HST2, HST3, HST4
S.p. Spbc16D10.07c, Spcc132.02, hst4
C.e. Sir-2.1, F46G10.3, F46G10.7, C06A5.3
D.m. sir2, CG6284, CG3187
M.m. SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6
H.s. SIRT1, SIRT3, SIRT2, SIRT5, SIRT4
R.n. SIRT2
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]
Bryk, M., Banerjee, M., Murphy, M., Knudsen, K. E., Garfinkel, D. J., and Curcio, M. J. (1997). Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes Dev 11, 255-69. [Abstract]
Gottlieb, S., and Esposito, R. E. (1989). A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56, 771-6. [Abstract]
Imai, S., Armstrong, C. M., Kaeberlein, M., and Guarente, L. (2000). Transcriptional silencing and longevity protein Sir2 is an NAD- dependent histone deacetylase. Nature 403, 795-800. [Abstract]
Lin, S. J., Defossez, P. A., and Guarente, L. (2000). Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289, 2126-8. [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]
Shore, D., Squire, M., and Nasmyth, K. A. (1984). Characterization of two genes required for the position-effect control of yeast mating-type genes. Embo J 3, 2817-23. [Abstract]
Smith, J. S., and Boeke, J. D. (1997). An unusual form of transcriptional silencing in yeast ribosomal DNA. Genes Dev 11, 241-54. [Abstract]
Tanny, J. C., Dowd, G. J., Huang, J., Hilz, H., and Moazed, D. (1999). An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell 99, 735-45. [Abstract]
Tissenbaum, H. A., and Guarente, L. (2001). Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230. [Abstract]
Kaeberlein, M., Andalis, A. A., Fink, G. R., and Guarente, L. (2002). High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction. Mol Cell Biol 22, 8056-66. [Abstract]
Lin, S. J., Kaeberlein, M., Andalis, A. A., Sturtz, L. A., Defossez, P. A., Culotta, V. C., Fink, G. R., and Guarente, L. (2002). Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418, 344-8. [Abstract]
Relevant LinksSGD: http://genome-www4.stanford.edu/cgi-bin/SGD/locus.pl?locus=SIR2
Keywordscaloric restriction, calorie restriction, CR, rDNA, silencing, recombination, telomeres, sterility, yeast, replicative senescence, Saccharomyces, cerevisiae, chromatin, DNA, metabolism, NAD, nucleolus, non-homologous end-joining, transcription