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Genomes and Genes | SIR2SummaryGene Symbol: SIR2 Description: Sir2p Alias: MAR1 Species: Top Publications
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New alleles of SIR2 define cell-cycle-specific silencing functionsMirela Matecic
Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA
Genetics 173:1939-50. 2006..b>Sir2 is a protein deacetylase that is required for gene silencing in yeast...- Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylaseS Imai
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
Nature 403:795-800. 2000Yeast Sir2 is a heterochromatin component that silences transcription at silent mating loci, telomeres and the ribosomal DNA, and that also suppresses recombination in the rDNA and extends replicative life span... - A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNAS Gottlieb
Committee on Genetics, University of Chicago, Illinois 60637
Cell 56:771-6. 1989The 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... - Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome lossS G Holmes
Department of Molecular Biology, Princeton University, New Jersey 08544, USA
Genetics 145:605-14. 1997..We have investigated the functions and interactions of the Sir2, Sir3, and Sir4 proteins by overexpressing them in yeast cells... - Role for perinuclear chromosome tethering in maintenance of genome stabilityKarim Mekhail
Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 456:667-70. 2008..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 .. - Steps in assembly of silent chromatin in yeast: Sir3-independent binding of a Sir2/Sir4 complex to silencers and role for Sir2-dependent deacetylationGeorg J Hoppe
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 22:4167-80. 2002Transcriptional 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... - The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylasesJ Landry
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794 5215, USA
Proc Natl Acad Sci U S A 97:5807-11. 2000Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms... - Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complexW Shou
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
Cell 97:233-44. 1999..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... - Distinct roles for the essential MYST family HAT Esa1p in transcriptional silencingAstrid S Clarke
Division of Biological Sciences, UCSD Cancer Center and Center for Molecular Genetics, University of California San Diego, La Jolla, CA 92093, USA
Mol Biol Cell 17:1744-57. 2006..Although mutants of both ESA1 and SIR2 have enhanced rates of rDNA recombination, esa1 effects are more modest yet result in distinct structural changes .. - Sir2p-dependent protein segregation gives rise to a superior reactive oxygen species management in the progeny of Saccharomyces cerevisiaeNika Erjavec
Department of Cell and Molecular Biology Microbiology, Goteborg University, Medicinaregatan 9C, 413 90 Goteborg, Sweden
Proc Natl Acad Sci U S A 104:10877-81. 2007..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... - Rapamycin increases rDNA stability by enhancing association of Sir2 with rDNA in Saccharomyces cerevisiaeCheol Woong Ha
School of Biological Sciences, Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University, Seoul 151 747, Republic of Korea
Nucleic Acids Res 39:1336-50. 2011..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... - SIR2 regulates recombination between different rDNA repeats, but not recombination within individual rRNA genes in yeastTakehiko Kobayashi
National Institute for Basic Biology, Okazaki, Japan
Cell 117:441-53. 2004It 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... - Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1Mingguang Li
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, School of Medicine, Jordan Hall, Box 800733, Charlottesville, VA 22908, USA
Mol Cell Biol 30:3329-41. 2010..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 .. - Transcription factor UAF, expansion and contraction of ribosomal DNA (rDNA) repeats, and RNA polymerase switch in transcription of yeast rDNAM Oakes
Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697 1700, USA
Mol Cell Biol 19:8559-69. 1999..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 .. - Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activityChristopher M Armstrong
Department of Biology, Massachussetts Institute of Technology, Cambridge, MA 02139, USA
Mol Biol Cell 13:1427-38. 2002The yeast SIR2 gene and many of its homologs have been identified as NAD(+)-dependent histone deacetylases... - Saccharomyces cerevisiae Esc2p interacts with Sir2p through a small ubiquitin-like modifier (SUMO)-binding motif and regulates transcriptionally silent chromatin in a locus-dependent mannerQun Yu
Department of Biology, University of Rochester, Rochester, New York 14627, USA
J Biol Chem 285:7525-36. 2010..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... - Contrasting roles of checkpoint proteins as recombination modulators at Fob1-Ter complexes with or without fork arrestBidyut K Mohanty
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
Eukaryot Cell 8:487-95. 2009..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... - Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeastFeng Xu
Department of Biological Chemistry, Geffen School of Medicine at UCLA, and the Molecular Biology Institute, Boyer Hall, 611 Young Drive East, Los Angeles, CA 90095, USA
Mol Cell 27:890-900. 2007..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 .. - The NAD(+)-dependent Sir2p histone deacetylase is a negative regulator of chromosomal DNA replicationDonald L Pappas
Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Genes Dev 18:769-81. 2004..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... - 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 silencingJulie Huang
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Genes Dev 17:2162-76. 2003..rDNA silencing is mediated by a Sir2-containing complex called RENT (regulator of nucleolar silencing and telophase exit)... - Budding yeast silencing complexes and regulation of Sir2 activity by protein-protein interactionsJason C Tanny
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Mol Cell Biol 24:6931-46. 2004Gene silencing in the budding yeast Saccharomyces cerevisiae requires the enzymatic activity of the Sir2 protein, a highly conserved NAD-dependent deacetylase... - The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencingChristopher J Fry
Program in Molecular Medicine, University of Massachusetts Medical School, Biotech 2, Suite 210, Worcester, MA 01605, USA
Mol Cell Biol 26:9045-59. 2006..Our study shows that structurally similar nucleosomal surfaces provide distinct functionalities in vivo and in vitro... - Sir2-independent life span extension by calorie restriction in yeastMatt Kaeberlein
Department of Genome Sciences, University of Washington, Seattle, Washington, USA
PLoS Biol 2:E296. 2004..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 .. - Genes determining yeast replicative life span in a long-lived genetic backgroundMatt Kaeberlein
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
Mech Ageing Dev 126:491-504. 2005..In addition, over-expression of SIR2 or growth on low glucose increased life span... - A nonhistone protein-protein interaction required for assembly of the SIR complex and silent chromatinAdam D Rudner
Harvard Medical School, Department of Cell Biology, 240 Longwood Ave, Boston, MA 02115, USA
Mol Cell Biol 25:4514-28. 2005Budding yeast silent chromatin, or heterochromatin, is composed of histones and the Sir2, Sir3, and Sir4 proteins... - A homotrimer-heterotrimer switch in Sir2 structure differentiates rDNA and telomeric silencingFabien Cubizolles
Department of Molecular Biology and NCCR Frontiers in Genetics, University of Geneva, CH 1211 Geneva 4, Switzerland
Mol Cell 21:825-36. 2006..A point mutation in the Sir2p core domain (sir2(P394L)) compromises selectively rDNA repression... - Bypassing Sir2 and O-acetyl-ADP-ribose in transcriptional silencingChia Ching Chou
Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA
Mol Cell 31:650-9. 2008The yeast Sir2/3/4 complex forms a heterochromatin-like structure that represses transcription... - Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number controlJonathan Houseley
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
EMBO J 26:4996-5006. 2007..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... - Sir2 and calorie restriction in yeast: a skeptical perspectiveMatt Kaeberlein
Department of Pathology, University of Washington, Seattle, WA 98195, USA
Ageing Res Rev 6:128-40. 2007Activation of Sir2-family proteins in response to calorie restriction (CR) has been proposed as an evolutionarily conserved mechanism for life span extension... - Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylasesJanet Mead
Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854 8020, USA
Mol Cell Biol 27:2466-75. 2007b>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... - Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeastMitsuhiro Tsuchiya
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
Aging Cell 5:505-14. 2006..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... - Nuclear export modulates the cytoplasmic Sir2 homologue Hst2Jeanne M Wilson
Division of Biological Sciences, Section of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, 0347, La Jolla, California 92093, USA
EMBO Rep 7:1247-51. 2006..The silent information regulator 2 (Sir2) family of NAD-dependent protein deacetylases influences transcription by targeting proteins such as histones, p53 .. - Bypassing the catalytic activity of SIR2 for SIR protein spreading in Saccharomyces cerevisiaeBo Yang
Department of Biochemistry, Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA
Mol Biol Cell 17:5287-97. 2006..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... - SIR2 modifies histone H4-K16 acetylation and affects superhelicity in the ARS region of plasmid chromatin in Saccharomyces cerevisiaeFrancesco Chiani
Dipartimento di Genetica e Biologia Molecolare, Universita di Roma La Sapienza, Rome, Italy
Nucleic Acids Res 34:5426-37. 2006The 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... - Rfm1, a novel tethering factor required to recruit the Hst1 histone deacetylase for repression of middle sporulation genesRon McCord
Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA
Mol Cell Biol 23:2009-16. 2003..These results suggest that Rfm1 is a specificity factor that targets the Hst1 deacetylase to a subset of Sum1-regulated genes... - SIR2-induced inviability is suppressed by histone H4 overexpressionMirela Matecic
Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut 06459, USA
Genetics 162:973-6. 2002We have identified histone H4 as a high-expression suppressor of Sir2-induced inviability in yeast cells... - Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activitiesS Ghidelli
Unit on Chromatin and Transcription, NICHD NIH, Building 18T, Room 106, 18 Library Drive, Bethesda, MD 20892, USA
EMBO J 20:4522-35. 2001..Finally, we demonstrate that the Sir2p-containing complexes bind nucleosomes efficiently and partially restrict accessibility of the linker DNA to enzymatic probes... - Silent information regulator protein complexes in Saccharomyces cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits its interaction with SIR3D Moazed
Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA
Proc Natl Acad Sci U S A 94:2186-91. 1997The SIR2, SIR3, and SIR4 silent information regulator proteins are involved in the assembly of silent chromatin domains in the budding yeast Saccharomyces cerevisiae... - A genetic screen for ribosomal DNA silencing defects identifies multiple DNA replication and chromatin-modulating factorsJ S Smith
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Mol Cell Biol 19:3184-97. 1999..TPE]) and the cryptic mating-type loci (HML and HMR) depends on the silent information regulator genes, SIR1, SIR2, SIR3, and SIR4... - Conversion of a gene-specific repressor to a regional silencerL N Rusché
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
Genes Dev 15:955-67. 2001..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... - Localization of Sir2p: the nucleolus as a compartment for silent information regulatorsM Gotta
Swiss Institute for Experimental Cancer Research, Chemin des Boveresses, Epalinges Lausanne, Switzerland
EMBO J 16:3243-55. 1997..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... - Analysis of Sir2p domains required for rDNA and telomeric silencing in Saccharomyces cerevisiaeM M Cockell
Swiss Institute for Experimental Cancer Research ISREC, CH 1066 Epalinges, Switzerland
Genetics 154:1069-83. 2000Silent information regulator (Sir) 2 is a limiting component of the Sir2/3/4 complex, which represses transcription at subtelomeric and HM loci... - Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiaeJ Xie
Waksman Institute and Department of Molecular Biology and Biochemistry, 190 Frelinghuysen Road, Rutgers University, Piscataway, NJ 08854 8020, USA
EMBO J 18:6448-54. 1999..NDT80 is regulated during mitosis by both the Sum1 and Ume6 repressors. These results suggest that progression through sporulation may be controlled by the regulated competition between the Sum1 repressor and Ndt80 activator at key MSEs... - A general requirement for the Sin3-Rpd3 histone deacetylase complex in regulating silencing in Saccharomyces cerevisiaeZ W Sun
Department of Biochemistry, Division of Nucleic Acids Enzymology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
Genetics 152:921-32. 1999..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)... - Net1, a Sir2-associated nucleolar protein required for rDNA silencing and nucleolar integrityA F Straight
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115 5730, USA
Cell 97:245-56. 1999The Sir2 protein mediates gene silencing and repression of recombination at the rDNA repeats in budding yeast... - The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stabilityC B Brachmann
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
Genes Dev 9:2888-902. 1995..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... - The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiaeS H Meijsing
Otto Warburg Laboratorium, Max Planck Institut fur Molekulare Genetik, D 14195 Berlin, Germany
Genes Dev 15:3169-82. 2001.... - hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiaeRobert J Merker
Department of Biochemistry and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA
Mol Cell Biol 22:421-9. 2002..The hpr1Delta mutant acts in a pathway distinct from previously described mutants that reduce life span... - Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein associationHuck Hui Ng
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Genes Dev 16:1518-27. 2002..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... - Telomeric and rDNA silencing in Saccharomyces cerevisiae are dependent on a nuclear NAD(+) salvage pathwayJoseph J Sandmeier
Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
Genetics 160:877-89. 2002The 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)... - Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatinNoriyuki Suka
Department of Biological Chemistry, UCLA School of Medicine and the Molecular Biology Institute, Boyer Hall, University of California, Los Angeles, California 90095, USA
Nat Genet 32:378-83. 2002..These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin... - Sir2 represses endogenous polymerase II transcription units in the ribosomal DNA nontranscribed spacerChonghua Li
Department of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843, USA
Mol Biol Cell 17:3848-59. 2006..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 .. - Evidence that Set1, a factor required for methylation of histone H3, regulates rDNA silencing in S. cerevisiae by a Sir2-independent mechanismMary Bryk
Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
Curr Biol 12:165-70. 2002..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-.. - Dual roles for Mcm10 in DNA replication initiation and silencing at the mating-type lociNancy L Douglas
Department of Molecular Biology and Genetics, Cornell University, 327 Biotechnology Building, Ithaca, NY 14853 2703, USA
Mol Biol Rep 32:197-204. 2005..Our findings, that Mcm10 mutants disrupt mating loci silencing and that Mcm10 interacts with Sir2 and Sir3, suggest that Mcm10 also plays an essential, and separable role in transcriptional silencing. - The implication of Sir2 in replicative aging and senescence in Saccharomyces cerevisiaeCheol Woong Ha
School of Biological Sciences, Research Center for Functional Cellulomics, Institute of Microbiology, Seoul National University, Republic of Korea
Aging (Albany NY) 3:319-24. 2011..In Saccharomyces cerevisiae, silent information regulator 2 (Sir2) modulates cellular senescence... - The sporulation capable (sca) mutation of Saccharomyces cerevisiae is an allele of the SIR2 geneJ P Margolskee
Department of Biochemistry of Biophysics, University of California, San Francisco
Mol Gen Genet 211:430-4. 1988..We have found further that sca is an allele of SIR2, one of the genes involved in repression of the silent cassettes... - Sir2 links chromatin silencing, metabolism, and agingL Guarente
Department of Biology, Massachusetts Institute of Technology (MIT, Cambridge, Massachusetts 02139 USA
Genes Dev 14:1021-6. 2000 - Mek1 suppression of meiotic double-strand break repair is specific to sister chromatids, chromosome autonomous and independent of Rec8 cohesin complexesTracy L Callender
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794 5215, USA
Genetics 185:771-82. 2010..The pattern of DSB repair in haploids containing Dmc1 and/or Rad51 indicates that Mek1 acts on Rad51-specific recombination processes... - Histone H3 Lys79 methylation is required for efficient nucleotide excision repair in a silenced locus of Saccharomyces cerevisiaeShubho Chaudhuri
Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA 99164 4660, USA
Nucleic Acids Res 37:1690-700. 2009..there is enhanced recruitment of the Sir complex at the HML locus of these mutants, and deletion of the SIR2 or SIR3 genes restores the MNase accessibility and DNA repair efficiency at this locus... - Structural basis for the role of the Sir3 AAA+ domain in silencing: interaction with Sir4 and unmethylated histone H3K79Stefan Ehrentraut
Abteilung fur Genetik, Zentrum für Medizinische Biotechnologie ZMB, Universitat Duisburg Essen, D 45141 Essen, Germany
Genes Dev 25:1835-46. 2011The silent information regulator 2/3/4 (Sir2/3/4) complex is required for gene silencing at the silent mating-type loci and at telomeres in Saccharomyces cerevisiae... - Sir2, caloric restriction and agingStewart Frankel
Pathol Biol (Paris) 54:55-7. 2006 - SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeastS Strahl-Bolsinger
Department of Biological Chemistry, University of California, Los Angeles 90095, USA
Genes Dev 11:83-93. 1997Yeast 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... - The sum1-1 mutation affects silent mating-type gene transcription in Saccharomyces cerevisiaeG P Livi
Cold Spring Harbor Laboratory, New York 11724
Mol Cell Biol 10:409-12. 1990..The sum1-1 mutation was previously identified as an extragenic suppressor of mutations in MAR1 (SIR2) and MAR2 (SIR3)... - Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediatesFuyang Li
Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA
Mol Cell 30:325-35. 2008..Deletion of SAW1 abolished association of Rad1 at SSA intermediates in vivo. We propose that Saw1 targets Rad1/Rad10 to Rad52-coated recombination intermediates... - A yeast sir2 mutant temperature sensitive for silencingChia Lin Wang
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794 5215, USA
Genetics 180:1955-62. 2008..Saccharomyces cerevisiae temperature-sensitive silencing mutants identified a strain with a point mutation in the SIR2 gene. The mutation changed Ser276 to Cys... - A SUMO-like domain protein, Esc2, is required for genome integrity and sister chromatid cohesion in Saccharomyces cerevisiaeTomoko Ohya
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Genetics 180:41-50. 2008.... - Mcm10 mediates the interaction between DNA replication and silencing machineriesIvan Liachko
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Genetics 181:379-91. 2009..helicase (Mcm3 and Mcm7) play a role in silencing and physically interact with the essential silencing factor, Sir2, even in the absence of DNA replication... - Histone deacetylase Rpd3 antagonizes Sir2-dependent silent chromatin propagationJing Zhou
The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Institutes for Biological Sciences, Chinese Academy of Sciences, The Graduate School, Shanghai 200031, China
Nucleic Acids Res 37:3699-713. 2009..Together, these data provide insight into the molecular mechanisms for the anti-silencing functions of Rpd3p during the formation of heterochromatin boundaries... - Telomere recombination accelerates cellular aging in Saccharomyces cerevisiaeXiao Fen Chen
The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People s Republic of China
PLoS Genet 5:e1000535. 2009..These results suggest that telomere recombination accelerates cellular aging in telomerase-null type II survivors and that telomerase is likely a superior telomere maintenance pathway in sustaining yeast replicative life span... - [Sir2 gene]Hidetaka Ota
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo
Nihon Rinsho 67:1289-92. 2009..We discuss a potential therapeutic target, Sirt1 and challenge for prevention of age-related diseases (Alzheimer's dementia, osteoporosis, sarcopenia, arteriosclerosis and cancer)... - Reconstitution of heterochromatin-dependent transcriptional gene silencingAaron Johnson
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Mol Cell 35:769-81. 2009Heterochromatin assembly in budding yeast requires the SIR complex, which contains the NAD-dependent deacetylase Sir2 and the Sir3 and Sir4 proteins... - Differential participation of homologous recombination and nucleotide excision repair in yeast survival to ultraviolet light radiationMartin Toussaint
Departement de Microbiologie et d Infectiologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada
Mutat Res 698:52-9. 2010..Additional aims were to study the participation of HR and NER in promoting UV survival during the cell cycle, and to define the extent of the co-participation for both repair pathways... - Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2Russell P Darst
Department of Molecular Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0347, USA
Mol Cell Biol 28:1361-72. 2008The broadly conserved Sir2 NAD(+)-dependent deacetylase is required for chromatin silencing... - An ARS element inhibits DNA replication through a SIR2-dependent mechanismAmber Crampton
Laboratory of Chromosome Replication, Van Andel Research Institute, Grand Rapids, MI 49503, USA
Mol Cell 30:156-66. 2008..Here, we identified five SIR2-sensitive origins on chromosomes III and VI... - Evolution of new function through a single amino acid change in the yeast repressor Sum1pAlexias Safi
Institute for Genome Sciences and Policy, Box 3382, Duke University, Durham, NC 27710, USA
Mol Cell Biol 28:2567-78. 2008..In addition, self-association of chromatin proteins may promote the formation of extended chromatin structures... - Telomerase-independent proliferation is influenced by cell type in Saccharomyces cerevisiaeJoanna E Lowell
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309 0215, USA
Genetics 164:909-21. 2003..We propose that cell-type-specific regulation of recombination at human telomeres may similarly contribute to the tissue-specific patterns of disease found in telomerase-deficient tumors... - The Rtf1 component of the Paf1 transcriptional elongation complex is required for ubiquitination of histone H2BHuck Hui Ng
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 278:33625-8. 2003..Rtf1 is important for telomeric silencing, with loss of H3-Lys4 and H3-Lys79 methylation synergistically reducing Sir2 association with telomeric DNA... - Mutations in DNA replication genes reduce yeast life spanLaura L Mays Hoopes
Braun Laboratories, California Institute of Technology, Pasadena, California 91125, USA
Mol Cell Biol 22:4136-46. 2002..In addition, the life span of dna2 mutants is extended by expression of an additional copy of SIR2 or by deletion of FOB1, which also increase wild-type life span... - Tandem bromodomains in the chromatin remodeler RSC recognize acetylated histone H3 Lys14Margaret Kasten
Howard Hughes Medical Institute and Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
EMBO J 23:1348-59. 2004..Taken together, Rsc4 bears essential tandem bromodomains that rely on H3 Lys14 acetylation to assist RSC complex for gene activation... - Dicentric chromosome stretching during anaphase reveals roles of Sir2/Ku in chromatin compaction in budding yeastD A Thrower
Department of Biology, CB3280 University of North Carolina, Chapel Hill, NC 27599 3280, USA
Mol Biol Cell 12:2800-12. 2001We have used mitotic spindle forces to examine the role of Sir2 and Ku in chromatin compaction... - Net1 stimulates RNA polymerase I transcription and regulates nucleolar structure independently of controlling mitotic exitW Shou
Division of Biology, California Institute of Technology, Pasadena 91125, USA
Mol Cell 8:45-55. 2001The budding yeast RENT complex, consisting of at least three proteins (Net1, Cdc14, Sir2), is anchored to the nucleolus by Net1. RENT controls mitotic exit, nucleolar silencing, and nucleolar localization of Nop1... - The nuclear GTPase Gsp1p can affect proper telomeric function through the Sir4 protein in Saccharomyces cerevisiaeMartin Clement
Departement de Microbiologie et Immunologie, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec H3C 3J7, Canada
Mol Microbiol 62:453-68. 2006..Interestingly, Gsp1p was found to interact genetically and physically with the telomeric component Sir4p. Taken together, these results suggest that the GSP1 pathway could regulate proper telomeric function in yeast through Sir4p... - Requirement for the SRS2 DNA helicase gene in non-homologous end joining in yeastV Hegde
Department of Biochemistry and Kaplan Cancer Center, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Nucleic Acids Res 28:2779-83. 2000..Efficient NHEJ of sticky ends requires the Ku70 and Ku80 proteins and the silencing genes SIR2, SIR3 and SIR4... - Valproate induces apoptosis by inducing accumulation of neutral lipids which was prevented by disruption of the SIR2 gene in Saccharomyces cerevisiaeQi Sun
Department of Biochemistry 2nd, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuou, Yamanashi 409 3898, Japan
FEBS Lett 581:3991-5. 2007..VPA (20 mM) induced apoptosis in several HDAC mutants, including PRD3 and HDA1-disrupted cells and SIR2 over expressing cells, as well as in wild-type cells but not SIR2-disrupted cells... - Substitution as a mechanism for genetic robustness: the duplicated deacetylases Hst1p and Sir2p in Saccharomyces cerevisiaeMeleah A Hickman
Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America
PLoS Genet 3:e126. 2007..Our results imply that after the duplication, SIR2 and HST1 subfunctionalized... - Spreading of Sir3 protein in cells with severe histone H3 hypoacetylationArnold Kristjuhan
Mechanisms of Transcription Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom
Proc Natl Acad Sci U S A 100:7551-6. 2003..relationship between acetylation and the association of proteins such as Sir3, Sir4, and the histone deacetylase Sir2 with chromatin is still unclear... - Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104pNika Erjavec
Department of Cell and Molecular Biology, Goteborg University, 413 90 Goteborg, Sweden
Genes Dev 21:2410-21. 2007..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... - Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1Gemma Reverter-Branchat
Bioquímica de l Estrès Oxidatiu, Departament de Ciencies Mediques Basiques, IRBLLEIDA, Universitat de Lleida, 25008 Lleida, Spain
Microbiology 153:3667-76. 2007..In addition, 2xADH1 cells displayed an increased activity of silent information regulator 2 (Sir2)p, an NAD+-dependent histone deacetylase, due to a higher NAD+/NADH ratio... - Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiaeY Tsukamoto
Department of Molecular Biology, Institute of Medical Science, University of Tokyo, Japan
Nature 388:900-3. 1997..b>Sir2 and Sir3, but not Sir1, were also found to participate in these processes... - Conversion of a replication origin to a silencer through a pathway shared by a Forkhead transcription factor and an S phase cyclinLaurieann Casey
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Mol Biol Cell 19:608-22. 2008..Sir1 in turn helps establish silencing by stabilizing binding of the other Sir proteins, Sir2-4... - SUM1, an apparent positive regulator of the cryptic mating-type loci in Saccharomyces cerevisiaeA J Klar
Genetics 111:745-58. 1985..between the MAR/SIR gene products and to find new regulatory loci, we sought extragenic suppressors of the mar1-1 mutation... - Involvement of Sir2/4 in silencing of DNA breakage and recombination on mouse YACs during yeast meiosisYair Klieger
Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
Mol Biol Cell 16:1449-55. 2005..In meiotic yeast cells carrying the mutations sir2 or sir4, but not sir3, these YACs show DSBs, suggesting that a unique chromatin structure of the YACs, involving .. - Assembly of the SIR complex and its regulation by O-acetyl-ADP-ribose, a product of NAD-dependent histone deacetylationGunn Guang Liou
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Cell 121:515-27. 2005Assembly 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... - Mcm10 is required for the maintenance of transcriptional silencing in Saccharomyces cerevisiaeIvan Liachko
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
Genetics 171:503-15. 2005.... - Yeast Pch2 promotes domainal axis organization, timely recombination progression, and arrest of defective recombinosomes during meiosisG Valentin Börner
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 105:3327-32. 2008..We further propose that regulatory surveillance of normal and abnormal interchromosomal interactions in mitotic and meiotic cells may involve "structure-dependent interchromosomal interaction" (SDIX) checkpoints...
Research Grants
- NAD Biosynthesis and the Regulation of SirtuinsJEFFREY SCOTT SMITH; Fiscal Year: 2010..We have also recently identified thiamine biosynthesis as a metabolic pathway controlled by the Sir2 and Hst1 Sirtuins in response to changes in NAD and nicotinamide concentrations...
- Calorie Restriction-Mediated Life Span Extension in YeastJeffrey Smith; Fiscal Year: 2007..b>SIR2 is a central player in the regulation of yeast RLS and calorie restriction, but is not a key regulator of ..
- Control of Sir2 by Nuclear NAD Salvage PathwaysJeffrey Smith; Fiscal Year: 2007..For example, the Sir2 family of NAD-dependent protein deacetylases (the Sirtuins) couple the deacetylation of specific acetyl-lysine side ..
- Function of Mammalian SIRT1 in AgingLeonard Guarente; Fiscal Year: 2007The aim of this proposal is to understand the molecular basis of aging by SIR2 genes in mammals. This gene determines the life span in yeast and C. elegans...
- CELL SENESCENCE IN SACCHAROMYCES CEREVISIAELeonard Guarente; Fiscal Year: 2007..granting period, we have identified genes and pathways that determine the life span ofyeast mother cells, including SIR2 and SSD1...
- Molecular Study of sir-2 genes and Aging in C. elegansLeonard Guarente; Fiscal Year: 2006..One of the genes that determines longevity in yeast and C. elegans (roundworms) is SIR2. The greater the activity of SIR2, the longer the life span in these organisms...
- Mechanisms of Life Span Extension By Dietary DeprivationMatt Kaeberlein; Fiscal Year: 2010..These studies will identify candidate therapeutic targets for several age-associated human diseases, including cancer, heart disease, diabetes, and Alzheimer's disease. ..
- Calorie Restriction-Mediated Life Span Extension in YeastJEFFREY SCOTT SMITH; Fiscal Year: 2010..b>SIR2 is a central player in the regulation of yeast RLS and calorie restriction, but is not a key regulator of ..
- Molecular Study of sir-2 genes and Aging in C. elegansLeonard P Guarente; Fiscal Year: 2010..The second is SIR2 and its related proteins (sirtuins), which have emerged in the past five years as important regulators of aging in ..
- Function of Mammalian SIRT1 in AgingLeonard P Guarente; Fiscal Year: 2010..We plan to determine the functions of mammalian sirtuins, with emphasis on SIRT1, in multiple cell types in mice. These studies may suggest new strategies to treat diseases of aging. ..
- Mechanisms of Life Span Extension By Dietary DeprivationMatt Kaeberlein; Fiscal Year: 2009..These studies will identify candidate therapeutic targets for several age-associated human diseases, including cancer, heart disease, diabetes, and Alzheimer's disease. ..
- THE RIBOSOMAL DNA AND TRANSCRIPTIONAL SILENCINGJeffrey Smith; Fiscal Year: 2004The long term objective of this proposal is to elucidate the molecular mechanism of rDNA silencing, which is the SIR2- dependent suppression of recombination and RNA polymerase II (Pol II)-mediated transcription in the yeast ribosomal DNA ..
- Analysis of rDNA Chromatin in Aging Yeast CellsJeffrey Smith; Fiscal Year: 2003..This approach is expected to yield important basic information about the link between aging and rDNA chromatin, and lead to an expanded RO1 application. ..
- CELL SENESCENCE IN SACCHAROMYCES CEREVISIAELeonard Guarente; Fiscal Year: 1993..The genes identified in these various genetic selections and screens will be cloned and sequenced. Functional relevance of these genes to aging, senescence, and cell death in higher organisms will be evaluated...
- MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGINGLeonard Guarente; Fiscal Year: 2003..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
- CELL SENESCENCE IN SACCHAROMYCES CEREVISIAELeonard Guarente; Fiscal Year: 2001....
- MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORSLeonard Guarente; Fiscal Year: 2001..Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically. ..