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Locus specificity determinants in the multifunctional yeast silencing protein Sir2
Author(s) -
Cuperus Guido,
Shafaatian Reza,
Shore David
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.11.2641
Subject(s) - biology , gene silencing , telomere , genetics , locus (genetics) , nucleolus , chromatin , subtelomere , mutant , histone , heterochromatin , saccharomyces cerevisiae , gene , cytoplasm
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.