Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast

Nucleic Acids Research
Abdul HannanKrishnaveni Mishra

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.

References

Feb 24, 1989·Cell·B J Thomas, R Rothstein
Jul 15, 1994·Structure·Y HarpazC Chothia
Jan 15, 1997·Genes & Development·J S Smith, J D Boeke
Jan 15, 1997·Genes & Development·M BrykM J Curcio
Jun 1, 1997·Current Opinion in Cell Biology·M Grunstein
Dec 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·D Shore
May 22, 2002·Protein Science : a Publication of the Protein Society·Wanyun Sheng, Xiubei Liao
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Dec 31, 2003·Methods in Enzymology·András Fiser, Andrej Sali
May 7, 2004·Genome Biology·Brian J North, Eric Verdin
Jun 11, 2004·Annual Review of Biochemistry·Gil Blander, Leonard Guarente
Aug 5, 2004·The Journal of Biological Chemistry·Vikram Govind PanseEd Hurt
Aug 25, 2004·The Journal of Biological Chemistry·James A WohlschlegelJohn R Yates
Dec 14, 2004·The Journal of Biological Chemistry·J Thomas HannichMark Hochstrasser
Dec 15, 2004·Molecular & Cellular Proteomics : MCP·Dennis D Wykoff, Erin K O'Shea
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xiaolan Zhao, Günter Blobel
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Oct 13, 2006·Molecular Biology of the Cell·Bo Yang, Ann L Kirchmaier
Nov 2, 2006·Journal of Cell Science·Alison ReindleErica S Johnson
Dec 19, 2007·Molecular and Cellular Biology·Russell P DarstLorraine Pillus
Apr 19, 2008·Cold Spring Harbor Symposia on Quantitative Biology·L Guarente
Nov 20, 2008·BMB Reports·Eun-Joo Kim, Soo-Jong Um
May 14, 2010·The Biochemical Journal·Kevin A Wilkinson, Jeremy M Henley
Jul 22, 2010·Molecular and Cellular Biology·Yaroslav SydorskyyBrian Raught
Oct 12, 2010·The International Journal of Biochemistry & Cell Biology·Jessica Barry, Richard B Lock
Nov 24, 2012·Nature Reviews. Molecular Cell Biology·Christopher M HickeyMark Hochstrasser
Nov 24, 2012·Biopolymers·Renee Garza, Lorraine Pillus
Jan 12, 2013·Genes & Development·Hao-Chi HsuRui-Ming Xu
Jan 19, 2013·Developmental Cell·Caelin Cubeñas-Potts, Michael J Matunis
May 29, 2013·Molecular Systems Biology·Tharan SrikumarBrian Raught
Jun 12, 2013·Annual Review of Biochemistry·Annette Flotho, Frauke Melchior
Aug 6, 2013·Biochemical and Biophysical Research Communications·Yakun WanZikai Zhou
Sep 11, 2013·Annual Review of Genetics·Stephanie KuengSusan M Gasser
Nov 26, 2013·Current Biology : CB·Ryo HiguchiLiza A Pon

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Citations

Dec 29, 2015·Nucleus·Amandine Bonnet, Benoit Palancade
Sep 9, 2017·The Journal of Cell Biology·Diego L LapetinaRichard W Wozniak
Aug 16, 2016·Genetics·Marc R Gartenberg, Jeffrey S Smith
Jan 28, 2021·ELife·Nikhil R BhagwatNeil Hunter

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Methods Mentioned

BETA
sumoylation
two-hybrid
PCR
pull down
pull-down
pull-downs
ChIP
immunoprecipitation
co-immunoprecipitation
2-hybrid

Software Mentioned

Zen
NAMD
HADDOCK
SASA
CHARMM
MODELLER

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