A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast

EMBO J. 2001 Jan 15;20(1-2):197-209. doi: 10.1093/emboj/20.1.197.

Abstract

In budding yeast, the silent information regulator Sir2p is a nuclear NAD-dependent deacetylase that is essential for both telomeric and rDNA silencing. All eukaryotic species examined to date have multiple homologues of Sir two (HSTs), which share a highly conserved globular core domain. Here we report that yeast Hst2p and a mammalian Hst2p homologue, hSirT2p, are cytoplasmic in yeast and human cells, in contrast to yHst1p and ySir2p which are exclusively nuclear. Although yHst2p cannot restore silencing in a sir2 deletion, overexpression of yHst2p influences nuclear silencing events in a SIR2 strain, derepressing subtelomeric silencing while increasing repression in the rDNA. In contrast, a form of ySir2p carrying a point mutation in the conserved core domain disrupts both telomeric position effect (TPE) and rDNA repression at low expression levels. This argues that non-nuclear yHst2p can compete for a substrate or ligand specifically required for telomeric, and not rDNA repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / chemistry
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism*
  • Amino Acid Substitution
  • Cell Nucleus / genetics*
  • Cytosol / enzymology
  • DNA, Fungal / genetics
  • DNA, Ribosomal / genetics
  • Gene Silencing*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phylogeny*
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Sirtuin 2
  • Sirtuins*
  • Telomere / genetics*

Substances

  • DNA, Fungal
  • DNA, Ribosomal
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Amidohydrolases
  • HST2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins