Article: article from journal or magazin.
A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast.
Publication types: Journal Article
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.
Amidohydrolases/chemistry, Amidohydrolases/genetics, 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, Sirtuins, Telomere/genetics
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