Recombinant Saccharomyces cerevisiae NAD-dependent histone deacetylase SIR2 (SIR2), partial

1. Excessive allocation of replication resources to origins within repetitive regions, induced by SIR2 deletion, leads to persistent replication gaps and genome instability. Conversely, the weakening of replication origins in repetitive regions suppresses these gaps. PMID: 28049846
2. We provide new mechanistic insights into Grx3/4 regulation of Sir2 by S-deglutathionylation to increase cell resistance to stress. This finding offers news perspectives on monothiol Grxs in redox signaling, describing Sir2 as a physiological substrate regulated by S-glutathionylation. PMID: 27085841
3. NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Delta cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. PMID: 27320176
4. Autophagy maintenance at homeostatic levels promoted by CR or TOR1 abrogation in syn-expressing cells was achieved by decreasing Sir2 levels and activity. Furthermore, the opposite function of Tor1 and Sir2 in autophagy is probably associated with the maintenance of autophagy activity at homeostatic levels PMID: 27109470
5. These genetic and biochemical studies support a model whereby Top1p recruits Sir2p to the rDNA and clarifies a structural role of DNA topoisomerase I in the epigenetic regulation of rDNA, independent of its known catalytic activity. PMID: 27825925
6. We provided evidence that these three patterns of MET3pr expression are caused by Sir2-mediated silencing, transcriptional interference, and 3D clustering. The clustering also occurs in the native genome and enhances the transcription of endogenous Met4-targeted genes. PMID: 28426659
7. Gcn5 is required for activation of nuclear genes and lifespan extension in the retrograde response.These results, along with the finding that the histone deacetylase Sir2 was required for a robust retrograde response informed a bioinformatics screen that reduced to four the candidate genes causal for longevity .Of the four, only deletion of PHO84 suppressed lifespan extension PMID: 27474729
8. Study identified two determinants of Sir2-mediated cohesion of silent chromatin: a cluster of charged residues on the surface of Sir2 and the Sir2-interacting factor Esc8. By mutating each of these factors, results show that robust silencing and cohesion are separable functions of silenced chromosomal domains. Interestingly, neither Esc8 nor the Sir2 surface is required for cohesin binding. PMID: 27185881
9. Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging. PMID: 28064165
10. The role of Sir2 for dietary restriction-mediated lifespan extension depends on cAMP-protein kinase A (PKA) and casein kinase 2 (CK2) signaling in yeast. PMID: 26329457
11. The findings demonstrate that sumoylation of Sir2 modulates distribution between telomeres and rDNA. PMID: 26319015
12. SIR-SIR interactions magnify the cooperativity in the Sir2-histone deacetylation positive feedback reaction and complete a double-negative feedback circuit involving antisilencing modifications. PMID: 25830651
13. Findings highlight the importance of the metabolic state of the cell in determining whether Sir2 can protect against or accelerate cellular aging of yeast PMID: 24997552
14. Sir2 shows genetic and physical interaction with Sgf73 of the SAGA complex. PMID: 25043177
15. This effect is specific, and the Sir2 deacetylase activity is required for the Sir2 mediated repression of NHP6A. Moreover, the presence of the SIR complex seems required for Sir2 to silence NHP6A. PMID: 25858320
16. Sir2 is upregulated by the unfolded protein response (UPR) but, in turn, it also attenuates this pathway, ensuring that UPR functions only transiently. PMID: 25600811
17. Thus, our findings suggest that proteasomes, Sir2, Snf1 and Hxk2 form an interconnected aging network that controls metabolism through coordinated regulation of Mig1. PMID: 25629410
18. SIRT1 gene is able to complement different molecular phenotypes of the sir2Delta mutant at rDNA PMID: 24349441
19. Cup9 overexpression represses SIR2 transcription and leads to a failure in the establishment of heterochromatin PMID: 25384977
20. In addition to genes involved in actin-dependent processes, SIR2-interactors required for asymmetrical inheritance of Htt103Q and heat-induced aggregates encode essential sec genes involved in ER-to-Golgi trafficking/ER homeostasis. PMID: 25079602
21. This position-dependent TAGEN also was dependent on Sir2p, an NAD+-dependent histone deacetylase PMID: 25057900
22. Loss of Gas1 promotes Sir2-mediated rDNA silencing by inducing the expression of Pnc1 in an Msn2/Msn4-dependent manner. PMID: 24981510
23. Results show that Rpd3 and Sir2 control replication timing in an opposite manner. Whereas Rpd3 delays initiation at late origins, Sir2 is required for the timely activation of early origins PMID: 24856221
24. genetic assay suggests that Tdh3, an NAD(+)-binding protein, influences nuclear NAD(+) levels; we speculate that Tdh3 links nuclear Sir2 with NAD(+) from the cytoplasm PMID: 24146631
25. activation of PKC-MAPK signaling by interruption of inositol sphingolipid synthesis leads to increased Sir2p-dependent silencing and is dependent upon the de novo and salvage pathways for NAD(+) synthesis but is not correlated with cellular NAD(+) levels PMID: 23943620
26. Data indicate that Rif1 maintains lifespan-sustaining levels of Sir2 at rDNA by preventing excessive recruitment of the histone deacetylase to telomeric and silent mating-type loci. PMID: 23082874
27. dependent aggregation was associated with increased cytotoxicity. We also show that two aging-related genes, SIR2 and HSF1, affect aggregation of the polyQ proteins PMID: 22970306
28. Sir2 functions as a regulator of autophagy. PMID: 22914317
29. the interaction between the Sir4 loop and the interdomain interface in Sir2 is critical for allosteric stimulation of the deacetylase activity of Sir2 PMID: 23307867
30. SIR2 deletion extended maximum chronological lifespan in wine yeasts grown under laboratory conditions, but shortened it in winemaking. Deletions of sirtuin HST2 and acetyltransferase GCN5 had the opposite effect to SIR2 mutation in both media. PMID: 22738658
31. Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration. PMID: 22539348
32. Data show that Sir2, and not Hst2, regulates the acetylation state of H3 lysine 79. PMID: 22474337
33. Reinventing heterochromatin in budding yeasts: Sir2 and the origin recognition complex take center stage PMID: 21764908
34. Among those 15, SIR2, HSP30, and TIM17 were upregulated in long-lived strains, which is consistent with the known effects of gene silencing, stress response, and mitochondrial function on aging PMID: 21306556
35. Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations in these interaction domains. PMID: 21690292
36. The deacetylation of H4K16(ac) by Sir2 actively promotes the high-affinity binding of the SIR holocomplex. PMID: 21666601
37. Discuss how Sir2 stabilizes rDNA under TOR inhibition and speculate on the link between sumoylation and Sir2-related pro-aging pathways. Review. PMID: 21415463
38. Data show that that inactivating SOV1, a member of the yeast mitochondrial translation control (MTC) module, causes a robust Sir2-dependent extension of replicative life span. PMID: 21549315
39. Taken together, these data define a unique role for Sir2 in cohesion of silent chromatin that is distinct from the enzyme's role as a histone deacetylase. PMID: 21304892
40. SIR2 mutants were shown to fail to maintain the mother-daughter asymmetry. PMID: 21084861
41. Orc1 functioned in silencing before duplication and Orc1 and Sir2 may have an ancient history of cooperating to generate chromatin structures, with Sir2 deacetylating histones and Orc1 binding to these deacetylated nucleosomes PMID: 20974972
42. These observations suggest that Sum1p is a novel regulator of microtubule function and as such, works independently from its binding partners Hst1 and Sir2 histone deacetylases. PMID: 20608984
43. Results identify a putative SUMO-binding motif in Esc2 that is necessary and sufficient for interacting with Sir2p and SUMO and is required for the function of Esc2p in transcriptional silencing. PMID: 20048165
44. mechanism for boundary formation at telomeres whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose PMID: 20133733
45. Data show that viability of mother cells in liquid culture is regulated by SIR2 and FOB1, two opposing regulators of RLS in yeast. PMID: 19652178
46. Sir2p does not have a role in caloric restriction-augmented reactive oxygen species defense PMID: 15875812
47. Extends longevity by overexpression. PMID: 15935564
48. The effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes. PMID: 16286010
49. The correlation of genetic and biochemical complementation argues that Sir2p trimerization is physiologically relevant for rDNA silencing. PMID: 16543151
50. Using a SIR2 temperature-sensitive allele, we show that silencing can be established at the HML locus during progression through the G2/M-G1 interval. PMID: 16783021

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KEGG: sce:YDL042C

STRING: 4932.YDL042C