Symbol: SIR2 Name: Silent Information Regulator 2 Alias: MAR1 Entrez gene ID: 851520 Ensembl gene ID: YDL042C Species: Yeast (Taxid: 4932) Functional description: Sir2 is a NAD(+)-dependent protein deacetylase which promotes transcriptional silincing at HM loci, telomeres and rDNA and represses recombination between rDNA repeats.; Sir2p; Conserved NAD+ dependent histone deacetylase of the Sirtuin family involved in regulation of lifespan; plays roles in silencing at HML, HMR, telomeres, and the rDNA locus; negatively regulates initiation of DNA replication [Source:SGD;Acc:S000002200] [Ensembl] Observation: Deletion of SIR2 shortens replicative lifespan by approximately 30%. Integration of a second copy of SIR2 into the wild-type strain leads to an extension of replicative lifespan by around 35% in W303R strain [10521401]. Deletion of SIR2 causes genomic instability at rDNA array [2647300] and shortens replicative lifespan by 50% [11000115]. 0.5% glucose restriction fails to increase the short lifespan of sir2Delta [11000115] probably duo to hyperaccumulations of extrachromosomal rDNA circles (ERCs) [16311627]. 0.1% glucose restriction extends replicative lifespan of sir2 mutants [12213553]. 0.5, 0.1 and 0.05% glucose restriction are able to increase lifespan of sir2;fob1 double mutant to a greater extent than in wild-type [15328540]. 0.05% glucose restriction further extends replicative lifespan of SIR2 overexpression mutant [15328540]. Sir2 blocks extreme chronological lifespan extension as the lack of Sir2 along with DR and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological lifespan extension (6-fold) [16286010]. Sir2 inhibits formation of ERCs and acts on histones as well metabolic enzymes among others. Overexpression extends replicative lifespan in several strains, but not in PSY316 [15684413]. Chronological lifespan of sir2 deletion mutant is significantly extended compared with wild-type in water (extreme DR) but not in saturated cultures containing 2% glucose (ad libitum). SIR2 mutants are defective for telomere [1913809] and HM silencing [6098447; 3297920]. have increased rDNA recombination [2647300] and a loss of rDNA silencing [9009207; 9009206]. Interventions: Assays: Replicative Lifespan Chronological Lifespan Classification: Aging Relevance Analysis/Source: Homologs Orthologs Note: Though Sir2 activity is detrimental for chronological lifespan extension. Sirtuins appear to have Pro- and Anti-Ageing activities. Edit \ Update (Admin) | Delete |
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