SIR2

Summary

Gene Symbol: SIR2
Description: NAD-dependent histone deacetylase SIR2
Alias: MAR1, NAD-dependent histone deacetylase SIR2
Species: Saccharomyces cerevisiae S288c
Products:     SIR2

Top Publications

  1. Matecic M, Martins Taylor K, Hickman M, Tanny J, Moazed D, Holmes S. New alleles of SIR2 define cell-cycle-specific silencing functions. Genetics. 2006;173:1939-50 pubmed
    ..b>Sir2 is a protein deacetylase that is required for gene silencing in yeast...
  2. Merker R, Klein H. hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiae. Mol Cell Biol. 2002;22:421-9 pubmed
    ..The hpr1Delta mutant acts in a pathway distinct from previously described mutants that reduce life span. ..
  3. Delaney J, Ahmed U, Chou A, Sim S, Carr D, Murakami C, et al. Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging. Aging Cell. 2013;12:156-66 pubmed publisher
    ..mRNA translation, enhanced resistance to tunicamycin that is independent of the ER unfolded protein response, and Sir2-independent but Gcn4-dependent lifespan extension...
  4. Jacobson S, Pillus L. The SAGA subunit Ada2 functions in transcriptional silencing. Mol Cell Biol. 2009;29:6033-45 pubmed publisher
    ..Ada2 binds telomeric chromatin and the silencing protein Sir2 in vivo...
  5. McClure J, Wierman M, Maqani N, Smith J. Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration. J Biol Chem. 2012;287:20957-66 pubmed publisher
    ..Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition...
  6. Ralser M, Zeidler U, Lehrach H. Interfering with glycolysis causes Sir2-dependent hyper-recombination of Saccharomyces cerevisiae plasmids. PLoS ONE. 2009;4:e5376 pubmed publisher
    ..Tdh2, and Tdh3) survived the counter-selection of a GAPDH-encoding plasmid when the NAD(+) metabolizing deacetylase Sir2 was overexpressed...
  7. Pappas D, Frisch R, Weinreich M. The NAD(+)-dependent Sir2p histone deacetylase is a negative regulator of chromosomal DNA replication. Genes Dev. 2004;18:769-81 pubmed
    ..Loss-of-function mutations in the chromatin-modifying genes SIR2, and to a lesser extent in SIR3 and SIR4, suppressed the cdc6-4 temperature-sensitive lethality...
  8. Rudner A, Hall B, Ellenberger T, Moazed D. A nonhistone protein-protein interaction required for assembly of the SIR complex and silent chromatin. Mol Cell Biol. 2005;25:4514-28 pubmed
    Budding yeast silent chromatin, or heterochromatin, is composed of histones and the Sir2, Sir3, and Sir4 proteins...
  9. Chiani F, Di Felice F, Camilloni G. SIR2 modifies histone H4-K16 acetylation and affects superhelicity in the ARS region of plasmid chromatin in Saccharomyces cerevisiae. Nucleic Acids Res. 2006;34:5426-37 pubmed
    The null mutation of the SIR2 gene in Saccharomyces cerevisiae has been associated with a series of different phenotypes including loss of transcriptional silencing, genome instability and replicative aging...

More Information

Publications79

  1. Gottlieb S, Esposito R. A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell. 1989;56:771-6 pubmed
    The yeast SIR2 gene is involved in regulating nucleosome phasing and transcription in the mating type system. We have found that SIR2 also plays another important role in the cell...
  2. Bryk M, Briggs S, Strahl B, Curcio M, Allis C, Winston F. Evidence that Set1, a factor required for methylation of histone H3, regulates rDNA silencing in S. cerevisiae by a Sir2-independent mechanism. Curr Biol. 2002;12:165-70 pubmed
    ..several lines of evidence that the role of Set1 in rDNA silencing is distinct from that of the histone deacetylase Sir2. Together, these results suggest that Set1-dependent H3 methylation is required for rDNA silencing in a Sir2-..
  3. Landry J, Sutton A, Tafrov S, Heller R, Stebbins J, Pillus L, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000;97:5807-11 pubmed
    Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms...
  4. Sun Z, Hampsey M. A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiae. Genetics. 1999;152:921-32 pubmed
    ..Enhanced silencing associated with sin3Delta, rpd3Delta, and sap30Delta is differentially dependent upon Sir2 and Sir4 at the telomeric and rDNA loci and is also dependent upon the ubiquitin-conjugating enzyme Rad6 (Ubc2)...
  5. Vendrell A, Martínez Pastor M, Gonzalez Novo A, Pascual Ahuir A, Sinclair D, Proft M, et al. Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase. EMBO Rep. 2011;12:1062-8 pubmed publisher
    ..Accumulation of Msn2 and Msn4 leads to the induction of PNC1, which is an activator of the Sir2 histone acetylase...
  6. Molin M, Yang J, Hanzén S, Toledano M, Labarre J, Nystrom T. Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae. Mol Cell. 2011;43:823-33 pubmed publisher
    ..is sufficient to extend the life span of cells grown in high glucose concentrations by 20% in a Tsa1-dependent and Sir2-independent manner...
  7. Johnson A, Li G, Sikorski T, Buratowski S, Woodcock C, Moazed D. Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol Cell. 2009;35:769-81 pubmed publisher
    Heterochromatin assembly in budding yeast requires the SIR complex, which contains the NAD-dependent deacetylase Sir2 and the Sir3 and Sir4 proteins...
  8. Cesarini E, D Alfonso A, Camilloni G. H4K16 acetylation affects recombination and ncRNA transcription at rDNA in Saccharomyces cerevisiae. Mol Biol Cell. 2012;23:2770-81 pubmed publisher
    ..Here we provide evidence that a single, rapid, and reversible posttranslational modification-the acetylation of the H4K16 residue-is involved in the coordination of transcription and recombination at rDNA. ..
  9. Xie J, Pierce M, Gailus Durner V, Wagner M, Winter E, Vershon A. Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae. EMBO J. 1999;18:6448-54 pubmed
    ..These results suggest that progression through sporulation may be controlled by the regulated competition between the Sum1 repressor and Ndt80 activator at key MSEs. ..
  10. Oppikofer M, Kueng S, Martino F, Soeroes S, Hancock S, Chin J, et al. A dual role of H4K16 acetylation in the establishment of yeast silent chromatin. EMBO J. 2011;30:2610-21 pubmed publisher
    ..Surprisingly, we found that the Sir2-4 subcomplex, unlike Sir3, has higher affinity for chromatin carrying H4K16(ac)...
  11. Belenky P, Racette F, Bogan K, McClure J, Smith J, Brenner C. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell. 2007;129:473-84 pubmed
    Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan...
  12. Hickman M, Rusche L. Substitution as a mechanism for genetic robustness: the duplicated deacetylases Hst1p and Sir2p in Saccharomyces cerevisiae. PLoS Genet. 2007;3:e126 pubmed
    ..Our results imply that after the duplication, SIR2 and HST1 subfunctionalized...
  13. Xu F, Zhang Q, Zhang K, Xie W, Grunstein M. Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast. Mol Cell. 2007;27:890-900 pubmed
    ..This cascade is believed to occur when Sir2, an NAD(+)-dependent enzyme, deacetylates histone H3 and H4 N termini, in particular histone H4 K16, enabling more ..
  14. Erjavec N, Larsson L, Grantham J, Nystrom T. Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p. Genes Dev. 2007;21:2410-21 pubmed
    ..Moreover, overproduction of Hsp104p suppressed the accelerated aging of cells lacking Sir2p, and drugs inhibiting damage segregation further demonstrated that spatial quality control is required to rejuvenate the progeny. ..
  15. McCord R, Pierce M, Xie J, Wonkatal S, Mickel C, Vershon A. Rfm1, a novel tethering factor required to recruit the Hst1 histone deacetylase for repression of middle sporulation genes. Mol Cell Biol. 2003;23:2009-16 pubmed
    ..These results suggest that Rfm1 is a specificity factor that targets the Hst1 deacetylase to a subset of Sum1-regulated genes. ..
  16. Kaeberlein M, Powers R. Sir2 and calorie restriction in yeast: a skeptical perspective. Ageing Res Rev. 2007;6:128-40 pubmed
    Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension...
  17. Martino F, Kueng S, Robinson P, Tsai Pflugfelder M, van Leeuwen F, Ziegler M, et al. Reconstitution of yeast silent chromatin: multiple contact sites and O-AADPR binding load SIR complexes onto nucleosomes in vitro. Mol Cell. 2009;33:323-34 pubmed publisher
    ..loci, chromatin assumes a higher-order structure that represses transcription by means of the histone deacetylase Sir2 and structural proteins Sir3 and Sir4...
  18. Tsukamoto Y, Kato J, Ikeda H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature. 1997;388:900-3 pubmed
    ..b>Sir2 and Sir3, but not Sir1, were also found to participate in these processes...
  19. Smith J, Caputo E, Boeke J. A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factors. Mol Cell Biol. 1999;19:3184-97 pubmed
    ..TPE]) and the cryptic mating-type loci (HML and HMR) depends on the silent information regulator genes, SIR1, SIR2, SIR3, and SIR4...
  20. Sandmeier J, Celic I, Boeke J, Smith J. Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD(+) salvage pathway. Genetics. 2002;160:877-89 pubmed
    The Sir2 protein is an NAD(+)-dependent protein deacetylase that is required for silencing at the silent mating-type loci, telomeres, and the ribosomal DNA (rDNA)...
  21. Smith D, Li C, Matecic M, Maqani N, Bryk M, Smith J. Calorie restriction effects on silencing and recombination at the yeast rDNA. Aging Cell. 2009;8:633-42 pubmed publisher
    ..Activation of the NAD(+)-dependent protein deacetylase Sir2 (Silent Information Regulator 2) has been proposed to mediate the beneficial effects of CR in the budding yeast ..
  22. Kobayashi T, Horiuchi T, Tongaonkar P, Vu L, Nomura M. SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeast. Cell. 2004;117:441-53 pubmed
    It is known that mutations in gene SIR2 increase and those in FOB1 decrease recombination within rDNA repeats as assayed by marker loss or extrachromosomal rDNA circle formation...
  23. Brachmann C, Sherman J, Devine S, Cameron E, Pillus L, Boeke J. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev. 1995;9:2888-902 pubmed
    ..We report here the discovery of four Saccharomyces cerevisiae homologs of the SIR2 silencing gene (HSTs), as well as conservation of this gene family from bacteria to mammals...
  24. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol. 2004;2:E296 pubmed
    ..In yeast, a mechanistic explanation has been proposed whereby calorie restriction slows aging by activating Sir2. Here we report the identification of a Sir2-independent pathway responsible for a majority of the longevity ..
  25. Ha C, Huh W. Rapamycin increases rDNA stability by enhancing association of Sir2 with rDNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2011;39:1336-50 pubmed publisher
    ..and nitrogen starvation, both of which cause inactivation of TOR complex 1 (TORC1), lead to enhanced association of Sir2 with ribosomal DNA (rDNA) in Saccharomyces cerevisiae...
  26. Huang J, Moazed D. Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing. Genes Dev. 2003;17:2162-76 pubmed
    ..rDNA silencing is mediated by a Sir2-containing complex called RENT (regulator of nucleolar silencing and telophase exit)...
  27. Shou W, Seol J, Baskerville C, Moazed D, Chen Z, Jang J, et al. Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell. 1999;97:233-44 pubmed
    ..RENT (for regulator of nucleolar silencing and telophase), that also contains Cdc14 and the silencing regulator Sir2. From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1...
  28. Li M, Petteys B, McClure J, Valsakumar V, Bekiranov S, Frank E, et al. Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1. Mol Cell Biol. 2010;30:3329-41 pubmed publisher
    ..NAD(+) concentration via the NAD(+)-dependent histone deacetylase (HDAC) Hst1 and, to a lesser extent, Sir2. Both of these HDACs associate with a distal region of the affected THI gene promoters that does not overlap with a ..
  29. Li C, Mueller J, Bryk M. Sir2 represses endogenous polymerase II transcription units in the ribosomal DNA nontranscribed spacer. Mol Biol Cell. 2006;17:3848-59 pubmed
    ..To explore how the silencing factor Sir2 regulates the composition and function of chromatin at the rDNA, the association of histones and RNA polymerase II ..
  30. Yu Q, Kuzmiak H, Olsen L, Kulkarni A, Fink E, Zou Y, et al. Saccharomyces cerevisiae Esc2p interacts with Sir2p through a small ubiquitin-like modifier (SUMO)-binding motif and regulates transcriptionally silent chromatin in a locus-dependent manner. J Biol Chem. 2010;285:7525-36 pubmed publisher
    ..Moreover, we dissect Esc2p and identify a putative SUMO-binding motif that is necessary and sufficient for interacting with Sir2p and SUMO and is required for the function of Esc2p in transcriptional silencing. ..
  31. Chou C, Li Y, Gartenberg M. Bypassing Sir2 and O-acetyl-ADP-ribose in transcriptional silencing. Mol Cell. 2008;31:650-9 pubmed publisher
    The yeast Sir2/3/4 complex forms a heterochromatin-like structure that represses transcription...
  32. Mekhail K, Seebacher J, Gygi S, Moazed D. Role for perinuclear chromosome tethering in maintenance of genome stability. Nature. 2008;456:667-70 pubmed publisher
    ..yeast Saccharomyces cerevisiae, that stability of the highly repetitive ribosomal DNA (rDNA) sequences requires a Sir2-containing chromatin silencing complex that also inhibits transcription from foreign promoters and transposons ..
  33. Cockell M, Perrod S, Gasser S. Analysis of Sir2p domains required for rDNA and telomeric silencing in Saccharomyces cerevisiae. Genetics. 2000;154:1069-83 pubmed
    Silent information regulator (Sir) 2 is a limiting component of the Sir2/3/4 complex, which represses transcription at subtelomeric and HM loci...
  34. Holmes S, Rose A, Steuerle K, Saez E, Sayegh S, Lee Y, et al. Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome loss. Genetics. 1997;145:605-14 pubmed
    ..We have investigated the functions and interactions of the Sir2, Sir3, and Sir4 proteins by overexpressing them in yeast cells...
  35. Liou G, Tanny J, Kruger R, Walz T, Moazed D. Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylation. Cell. 2005;121:515-527 pubmed publisher
    Assembly of silent chromatin domains in budding yeast involves the deacetylation of histone tails by Sir2 and the association of the Sir3 and Sir4 proteins with hypoacetylated histone tails...
  36. Fabrizio P, Gattazzo C, Battistella L, Wei M, Cheng C, McGrew K, et al. Sir2 blocks extreme life-span extension. Cell. 2005;123:655-67 pubmed
    b>Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging...
  37. Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics. 1987;116:9-22 pubmed
    ..Specifically, some recessive mutations in different genes fail to complement. The correspondence between SIR1, SIR2, SIR3, SIR4 and other genes with similar roles (MAR, CMT, STE8 and STE9) is presented.
  38. Ghidelli S, Donze D, Dhillon N, Kamakaka R. Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activities. EMBO J. 2001;20:4522-35 pubmed
    ..Finally, we demonstrate that the Sir2p-containing complexes bind nucleosomes efficiently and partially restrict accessibility of the linker DNA to enzymatic probes. ..
  39. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Genes determining yeast replicative life span in a long-lived genetic background. Mech Ageing Dev. 2005;126:491-504 pubmed
    ..In addition, over-expression of SIR2 or growth on low glucose increased life span...
  40. Clarke A, Samal E, Pillus L. Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencing. Mol Biol Cell. 2006;17:1744-57 pubmed
    ..Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA recombination, esa1 effects are more modest yet result in distinct structural changes ..
  41. Cubizolles F, Martino F, Perrod S, Gasser S. A homotrimer-heterotrimer switch in Sir2 structure differentiates rDNA and telomeric silencing. Mol Cell. 2006;21:825-36 pubmed
    ..A point mutation in the Sir2p core domain (sir2(P394L)) compromises selectively rDNA repression...
  42. Tsuchiya M, Dang N, Kerr E, Hu D, Steffen K, Oakes J, et al. Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging Cell. 2006;5:505-14 pubmed
    ..longevity in yeast: (i) suppression of rDNA recombination through activation of the sirtuin protein deacetylase Sir2 or (ii) decreased activity of the nutrient-responsive kinases Sch9 and TOR...
  43. Ha C, Sung M, Huh W. Nsi1 plays a significant role in the silencing of ribosomal DNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2012;40:4892-903 pubmed publisher
    ..In addition, Nsi1 physically interacts with the known rDNA silencing factors Net1, Sir2 and Fob1. The loss of Nsi1 decreases the association of Sir2 with NTS1 and increases histone acetylation at NTS1...
  44. Matecic M, Stuart S, Holmes S. SIR2-induced inviability is suppressed by histone H4 overexpression. Genetics. 2002;162:973-6 pubmed
    We have identified histone H4 as a high-expression suppressor of Sir2-induced inviability in yeast cells...
  45. Mohanty B, Bairwa N, Bastia D. Contrasting roles of checkpoint proteins as recombination modulators at Fob1-Ter complexes with or without fork arrest. Eukaryot Cell. 2009;8:487-95 pubmed publisher
    ..The work also showed that the two pathways were Rad52 dependent but Rad51 independent. Since Ter sites occur in the intergenic spacer of rDNA from yeast to humans, the mechanism is likely to be of widespread occurrence. ..
  46. Houseley J, Kotovic K, El Hage A, Tollervey D. Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control. EMBO J. 2007;26:4996-5006 pubmed
    ..Trf4 showed sporadic changes in rDNA copy number, whereas loss of both Trf4 and either the histone deacetylase Sir2 or the topoisomerase Top1 caused dramatic loss of rDNA repeats...
  47. Straight A, Shou W, Dowd G, Turck C, Deshaies R, Johnson A, et al. Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrity. Cell. 1999;97:245-56 pubmed
    The Sir2 protein mediates gene silencing and repression of recombination at the rDNA repeats in budding yeast...
  48. Sampaio Marques B, Felgueiras C, Silva A, RODRIGUES M, Tenreiro S, Franssens V, et al. SNCA (?-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2 (Sir2)-mediated mitophagy. Autophagy. 2012;8:1494-509 pubmed publisher
    ..Deletion of SIR2, essential for SNCA toxicity, abolished autophagy and mitophagy, thereby rescuing cells...
  49. Ehrentraut S, Weber J, Dybowski J, Hoffmann D, Ehrenhofer Murray A. Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate. Proc Natl Acad Sci U S A. 2010;107:5522-7 pubmed publisher
    ..suggest a mechanism for boundary formation whereby histone deacetylation by Rpd3 removes the substrate for the HDAC Sir2, so that Sir2 no longer can produce O-acetyl-ADP ribose (OAADPR) by consumption of NAD(+) in the deacetylation ..
  50. Suka N, Luo K, Grunstein M. Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nat Genet. 2002;32:378-83 pubmed
    ..These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin. ..
  51. Hoppe G, Tanny J, Rudner A, Gerber S, Danaie S, Gygi S, et al. Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylation. Mol Cell Biol. 2002;22:4167-80 pubmed
    Transcriptional silencing at the budding yeast silent mating type (HM) loci and telomeric DNA regions requires Sir2, a conserved NAD-dependent histone deacetylase, Sir3, Sir4, histones H3 and H4, and several DNA-binding proteins...
  52. Gotta M, Strahl Bolsinger S, Renauld H, Laroche T, Kennedy B, Grunstein M, et al. Localization of Sir2p: the nucleolus as a compartment for silent information regulators. EMBO J. 1997;16:3243-55 pubmed
    ..In strains lacking Sir4p, Sir3p becomes concentrated in the nucleolus, by a pathway requiring SIR2 and UTH4, a gene that regulates life span in yeast...
  53. Zhou J, Zhou B, Lenzmeier B, Zhou J. Histone deacetylase Rpd3 antagonizes Sir2-dependent silent chromatin propagation. Nucleic Acids Res. 2009;37:3699-713 pubmed publisher
    ..Together, these data provide insight into the molecular mechanisms for the anti-silencing functions of Rpd3p during the formation of heterochromatin boundaries. ..
  54. Meijsing S, Ehrenhofer Murray A. The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiae. Genes Dev. 2001;15:3169-82 pubmed
  55. Ng H, Feng Q, Wang H, Erdjument Bromage H, Tempst P, Zhang Y, et al. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev. 2002;16:1518-27 pubmed
    ..reflect an interaction between Sir proteins and Lys 79, because dot1 and Lys 79 mutations weaken the interaction of Sir2 and Sir3 with the telomeric region in vivo...
  56. Wilson J, Le V, Zimmerman C, Marmorstein R, Pillus L. Nuclear export modulates the cytoplasmic Sir2 homologue Hst2. EMBO Rep. 2006;7:1247-51 pubmed
    ..The silent information regulator 2 (Sir2) family of NAD-dependent protein deacetylases influences transcription by targeting proteins such as histones, p53 ..
  57. Oakes M, Siddiqi I, Vu L, Aris J, Nomura M. Transcription factor UAF, expansion and contraction of ribosomal DNA (rDNA) repeats, and RNA polymerase switch in transcription of yeast rDNA. Mol Cell Biol. 1999;19:8559-69 pubmed
    ..Mutations in genes that affect recombination within the rDNA repeats, fob1 and sir2, decrease and increase, respectively, the frequency of switching to growth using Pol II, indicating that increased ..
  58. Strahl Bolsinger S, Hecht A, Luo K, Grunstein M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 1997;11:83-93 pubmed
    Yeast core telomeric heterochromatin can silence adjacent genes and requires RAP1, SIR2, SIR3, and SIR4 and histones H3 and H4 for this telomere position effect. SIR3 overproduction can extend the silenced domain...
  59. Lynch P, Rusche L. An auxiliary silencer and a boundary element maintain high levels of silencing proteins at HMR in Saccharomyces cerevisiae. Genetics. 2010;185:113-27 pubmed publisher
  60. Rusché L, Rine J. Conversion of a gene-specific repressor to a regional silencer. Genes Dev. 2001;15:955-67 pubmed
    ..Sum1-1p-mediated silencing also depended on HST1, a paralog of SIR2. Both Sum1-1p and wild-type Sum1p interacted with Hst1p in coimmunoprecipitation experiments...
  61. Tanny J, Kirkpatrick D, Gerber S, Gygi S, Moazed D. Budding yeast silencing complexes and regulation of Sir2 activity by protein-protein interactions. Mol Cell Biol. 2004;24:6931-46 pubmed
    Gene silencing in the budding yeast Saccharomyces cerevisiae requires the enzymatic activity of the Sir2 protein, a highly conserved NAD-dependent deacetylase...
  62. Vasiljeva L, Kim M, Terzi N, Soares L, Buratowski S. Transcription termination and RNA degradation contribute to silencing of RNA polymerase II transcription within heterochromatin. Mol Cell. 2008;29:313-23 pubmed publisher
    Within the heterochromatin of budding yeast, RNA polymerase II (RNAPII) transcription is repressed by the Sir2 deacetylase...
  63. Erjavec N, Nystrom T. Sir2p-dependent protein segregation gives rise to a superior reactive oxygen species management in the progeny of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2007;104:10877-81 pubmed
    ..Such spatial quality control provides the daughter cells with a superior capacity to combat external oxidative stress and delays self-inflicted oxidative damage to their cellular proteins. ..
  64. Hickman M, McCullough K, Woike A, Raducha Grace L, Rozario T, Dula M, et al. Isolation and characterization of conditional alleles of the yeast SIR2 gene. J Mol Biol. 2007;367:1246-57 pubmed
    b>Sir2 is a protein deacetylase that mediates transcriptional silencing at the HM loci, telomeres, and rDNA repeats in yeast. To identify functionally significant regions of the Sir2 protein, we have characterized two types of mutations...
  65. Mead J, McCord R, Youngster L, Sharma M, Gartenberg M, Vershon A. Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases. Mol Cell Biol. 2007;27:2466-75 pubmed
    b>Sir2 and Hst1 are NAD(+)-dependent histone deacetylases of budding yeast that are related by strong sequence similarity. Nevertheless, the two proteins promote two mechanistically distinct forms of gene repression...
  66. Armstrong C, Kaeberlein M, Imai S, Guarente L. Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activity. Mol Biol Cell. 2002;13:1427-38 pubmed
    The yeast SIR2 gene and many of its homologs have been identified as NAD(+)-dependent histone deacetylases...
  67. Fry C, Norris A, Cosgrove M, Boeke J, Peterson C. The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing. Mol Cell Biol. 2006;26:9045-59 pubmed
    ..Our study shows that structurally similar nucleosomal surfaces provide distinct functionalities in vivo and in vitro. ..
  68. Wang C, Landry J, Sternglanz R. A yeast sir2 mutant temperature sensitive for silencing. Genetics. 2008;180:1955-62 pubmed publisher
    ..Saccharomyces cerevisiae temperature-sensitive silencing mutants identified a strain with a point mutation in the SIR2 gene. The mutation changed Ser276 to Cys...
  69. Peng J, Zhou J. The tail-module of yeast Mediator complex is required for telomere heterochromatin maintenance. Nucleic Acids Res. 2012;40:581-93 pubmed publisher
    ..Our study reveals a specific role of Mediator complex at the heterochromatic telomere and this function is specific to telomeres as it has no effect on the HMR locus. ..
  70. Yang B, Kirchmaier A. Bypassing the catalytic activity of SIR2 for SIR protein spreading in Saccharomyces cerevisiae. Mol Biol Cell. 2006;17:5287-97 pubmed
    ..at the HM loci and telomeres in cells containing a stably expressed, but catalytically inactive mutant of Sir2p, sir2-345p, plus histone mutants that mimic the hypoacetylated state normally created by Sir2p...