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Locus specificity determinants in the multifunctional yeast silencing protein Sir2

Shafaatian, Reza
Published in EMBO Journal. 2000, vol. 19, no. 11, p. 2641-2651
Abstract 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.
Keywords Chromatin/metabolism/ultrastructureFungal chromosomes/metabolism/ultrastructureFungal DNA/geneticsRibosomal DNA/geneticsFungal proteins/chemistry/metabolismGene silencingGene targetingDominant genesFungal genes/geneticsMating type fungal genesHistone deacetylases/chemistry/genetics/metabolismMacromolecular substancesMutagenesisOncogene proteins/metabolismPhenotypePolymerase chain reactionTertiary protein structureSaccharomyces cerevisiae/geneticsSaccharomyces cerevisiae silent information regulator proteinsSirtuin 2SirtuinsSubstrate specificityTelomere/geneticsTrans-activators/chemistry/genetics/metabolism
PMID: 10835361
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CUPERUS LENDORFF, Guido, SHAFAATIAN, Reza, SHORE, David M. Locus specificity determinants in the multifunctional yeast silencing protein Sir2. In: EMBO Journal, 2000, vol. 19, n° 11, p. 2641-2651. doi: 10.1093/emboj/19.11.2641 https://archive-ouverte.unige.ch/unige:127573

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Deposited on : 2019-12-06

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