Locus specificity determinants in the multifunctional yeast silencing protein Sir2

AUTOR(ES)

Cuperus, Guido

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Budding Yeast Silencing Complexes and Regulation of Sir2 Activity by Protein-Protein Interactions
• The Conserved Core of a Human SIR2 Homologue Functions in Yeast Silencing
• The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
• The Sir2 protein family: A novel deacetylase for gene silencing and more
• The Schizosaccharomyces pombe hst4+ Gene Is a SIR2 Homologue with Silencing and Centromeric Functions