title: Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast.
abstract: Silent information regulator 2 (Sir2), the founding member of the conserved sirtuin family of NAD(+)-dependent histone deacetylase, regulates several physiological processes including genome stability, gene silencing, metabolism and life span in yeast. Within the nucleus, Sir2 is associated with telomere clusters in the nuclear periphery and rDNA in the nucleolus and regulates gene silencing at these genomic sites. How distribution of Sir2 between telomere and rDNA is regulated is not known. Here we show that Sir2 is sumoylated and this modification modulates the intra-nuclear distribution of Sir2. We identify Siz2 as the key SUMO ligase and show that multiple lysines in Sir2 are subject to this sumoylation activity. Mutating K215 alone counteracts the inhibitory effect of Siz2 on telomeric silencing. SUMO modification of Sir2 impairs interaction with Sir4 but not Net1 and, furthermore, SUMO modified Sir2 shows predominant nucleolar localization. Our findings demonstrate that sumoylation of Sir2 modulates distribution between telomeres and rDNA and this is likely to have implications for Sir2 function in other loci as well.
authors: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors: Abdul
authors: A
authors: Hannan
authors: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors: Neethu Maria
authors: NM
authors: Abraham
authors: Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032, India.
authors: Siddharth
authors: S
authors: Goyal
authors: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors: Imlitoshi
authors: I
authors: Jamir
authors: Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032, India.
authors: U Deva
authors: UD
authors: Priyakumar
authors: Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India kmsl@uohyd.ernet.in.
authors: Krishnaveni
authors: K
authors: Mishra
mesh_terms: D002466:Cell Nucleolus / Q000378:metabolism; D004275:DNA, Ribosomal / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D016615:Telomere / Q000378:metabolism
chemical_list: D004275:DNA, Ribosomal; C061573:SIR4 protein, S cerevisiae; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D025841:Small Ubiquitin-Related Modifier Proteins; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D008239:Lysine