Locus specificity determinants in the multifunctional yeast silencing protein Sir2

Article Article scientifique Article Locus specificity determinants in the multifunctional yeast silencing protein Sir2 eng 2000 author Cuperus Lendorff Guido 89065 author Shafaatian Reza author Shore David M. 102587 2641-2651 10.1093/emboj/19.11.2641 10835361 0261-4189 Yeast SIR2, the founding member of a conserved gene family, acts to modulate chromatin structure in three different contexts: silent (HM) mating-type loci, telomeres and rDNA. At HM loci and telomeres, Sir2p forms a complex with Sir3p and Sir4p. However, Sir2p's role in rDNA silencing is Sir3/4 independent, requiring instead an essential nucleolar protein, Net1p. We describe two novel classes of SIR2 mutations specific to either HM/telomere or rDNA silencing. Despite their opposite effects, both classes of mutations cluster in the same two regions of Sir2p, each of which borders on a conserved core domain. A surprising number of these mutations are dominant. Several rDNA silencing mutants display a Sir2p nucleolar localization defect that correlates with reduced Net1p binding. Although the molecular defect in HM/telomere-specific mutants is unclear, they mimic an age-related phenotype where Sir3p and Sir4p relocalize to the nucleolus. Artificial targeting can circumvent the silencing defect in a subset of mutants from both classes. These results define distinct functional domains of Sir2p and provide evidence for additional Sir2p-interacting factors with locus-specific silencing functions. Chromatin/metabolism/ultrastructure Fungal chromosomes/metabolism/ultrastructure Fungal DNA/genetics Ribosomal DNA/genetics Fungal proteins/chemistry/metabolism Gene silencing Gene targeting Dominant genes Fungal genes/genetics Mating type fungal genes Histone deacetylases/chemistry/genetics/metabolism Macromolecular substances Mutagenesis Oncogene proteins/metabolism Phenotype Polymerase chain reaction Tertiary protein structure Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae silent information regulator proteins Sirtuin 2 Sirtuins Substrate specificity Telomere/genetics Trans-activators/chemistry/genetics/metabolism Dewey 570 43 Département de biologie moléculaire 161 false EMBO Journal 19 11 1e66315a-07d1-4f49-8722-f18f62f8c124 Article (Published version) Restricted cdd245.pdf 926990 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Locus specificity determinants in the multifunctional yeast silencing protein Sir2	EMBO Journal			2000	278	0

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Cuperus Lendorff, Guido