Locus specificity determinants in the multifunctional yeast silencing protein Sir2

Autor: Reza Shafaatian, David Shore, Guido Cuperus
Rok vydání: 2000
Předmět:
Nucleolus
Substrate specificity
Mutant
Tertiary protein structure
Mating type fungal genes
Trans-activators/chemistry/genetics/metabolism
Polymerase Chain Reaction
Fungal genes/genetics
Saccharomyces cerevisiae/genetics
Substrate Specificity
Sirtuin 2
Chromatin/metabolism/ultrastructure
Sirtuins
DNA
Fungal
Silent Information Regulator Proteins
Saccharomyces cerevisiae
Genes
Dominant
Genetics
Fungal proteins/chemistry/metabolism
Oncogene Proteins
General Neuroscience
Gene silencing
Articles
Telomere
Phenotype
Chromatin
Polymerase chain reaction
Fungal DNA/genetics
Macromolecular substances
Gene Targeting
Chromosomes
Fungal
Oncogene proteins/metabolism
Macromolecular Substances
Saccharomyces cerevisiae silent information regulator proteins
Genes
Fungal
Locus (genetics)
Saccharomyces cerevisiae
Biology
DNA
Ribosomal
General Biochemistry
Genetics and Molecular Biology
Histone Deacetylases
Fungal Proteins
Fungal chromosomes/metabolism/ultrastructure
ddc:570
Gene family
Gene Silencing
Molecular Biology
Telomere/genetics
General Immunology and Microbiology
Dominant genes
Gene targeting
Genes
Mating Type
Fungal
Protein Structure
Tertiary
Mutagenesis
Trans-Activators
Ribosomal DNA/genetics
Histone deacetylases/chemistry/genetics/metabolism
Zdroj: EMBO Journal, Vol. 19, No 11 (2000) pp. 2641-2651
Scopus-Elsevier
ISSN: 0261-4189
Popis: 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.
Databáze: OpenAIRE
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