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A cytosolic NAD‐dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast
Author(s) -
Perrod Séverine,
Cockell Moira M.,
Laroche Thierry,
Renauld Hubert,
Ducrest AnneLyse,
Bonnard Claude,
Gasser Susan M.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.197
Subject(s) - biology , yeast , saccharomyces cerevisiae , cytosol , gene silencing , nad+ kinase , nucleolus , genetics , microbiology and biotechnology , biochemistry , gene , enzyme , cytoplasm
In budding yeast, the s ilent i nformation r egulator Sir2p is a nuclear NAD‐dependent deacetylase that is essential for both telomeric and rDNA silencing. All eukaryotic species examined to date have multiple h omologues of S ir t wo (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.