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Nucleic Acids Res. 2015 Dec 2;43(21):10213-26. doi: 10.1093/nar/gkv842. Epub 2015 Aug 28.

Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast.

Author information

1
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
2
Center for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad 500032, India.
3
Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India kmsl@uohyd.ernet.in.

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.

PMID:
26319015
PMCID:
PMC4666389
DOI:
10.1093/nar/gkv842
[Indexed for MEDLINE]
Free PMC Article

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