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PMID: 10835361 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Locus specificity determinants in the multifunctional yeast silencing protein Sir2.

The EMBO journal ·Vol. 19 ·No. 11 ·2000-06-01 ·Pages 2641-51

Cuperus G, Shafaatian R, Shore D

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.

MeSH Terms
Chromatin/metabolism,ultrastructure Chromosomes, Fungal/metabolism,ultrastructure DNA, Fungal/genetics DNA, Ribosomal/genetics Fungal Proteins/chemistry,metabolism Gene Silencing Gene Targeting Genes, Dominant Genes, Fungal/genetics Genes, Mating Type, Fungal Histone Deacetylases/chemistry,genetics,metabolism Macromolecular Substances Mutagenesis Oncogene Proteins/metabolism Phenotype Polymerase Chain Reaction Protein Structure, Tertiary Saccharomyces cerevisiae/genetics Silent Information Regulator Proteins, Saccharomyces cerevisiae Sirtuin 2 Sirtuins Substrate Specificity Telomere/genetics Trans-Activators/chemistry,genetics,metabolism
Chemicals
Chromatin DNA, Fungal DNA, Ribosomal Fungal Proteins Macromolecular Substances Oncogene Proteins SIR3 protein, S cerevisiae SIR4 protein, S cerevisiae Silent Information Regulator Proteins, Saccharomyces cerevisiae Trans-Activators SIR2 protein, S cerevisiae Sirtuin 2 Sirtuins Histone Deacetylases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cuperus G
Department of Molecular Biology, University of Geneva, Geneva 4, CH-1211 Switzerland.
Shafaatian R
Shore D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.11.2641
Published
2000-06-01
Pages
2641-51
Language
English
Region
England
NLM ID
8208664
PMCID
PMC212746
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.11.2641 PMC Full Text View journal details
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