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Originally published as Genetics Published Articles Ahead of Print on November 15, 2004.
Genetics, Vol. 169, 1243-1260, March 2005, Copyright © 2005
doi:10.1534/genetics.104.032714
Conserved Locus-Specific Silencing Functions of Schizosaccharomyces pombe sir2+
Lisa L. Freeman-Cook*,1,
Eliana B. Gómez
,2,
Erik J. Spedale*,
John Marlett,
Susan L. Forsburg,2,
Lorraine Pillus*,3 and
Patricia Laurenson*
* Division of Biological Sciences, Section of Molecular Biology and UCSD Center for Cancer Research, University of California, San Diego, California 92093-0347
Molecular and Cell Biology Laboratory, The Salk Institute, La Jolla, California 92037
3 Corresponding author: Pacific Hall 2100A MC 0347, 9500 Gilman Dr., University of California, San Diego, CA 92093-0347.
E-mail: lpillus{at}biomail.ucsd.edu
In Schizosaccharomyces pombe, three genes, sir2+, hst2+, and hst4+, encode members of the Sir2 family of conserved NAD+-dependent protein deacetylases. The S. pombe sir2+ gene encodes a nuclear protein that is not essential for viability or for resistance to treatment with UV or a microtubule-destabilizing agent. However, sir2+ is essential for full transcriptional silencing of centromeres, telomeres, and the cryptic mating-type loci. Chromatin immunoprecipitation results suggest that the Sir2 protein acts directly at these chromosomal regions. Enrichment of Sir2p at silenced regions does not require the HP1 homolog Swi6p; instead, Swi6-GFP localization to telomeres depends in part on Sir2p. The phenotype of sir2 swi6 double mutants supports a model whereby Sir2p functions prior to Swi6p at telomeres and the silent mating-type loci. However, Sir2p does not appear to be essential for the localization of Swi6p to centromeric foci. Cross-complementation experiments showed that the Saccharomyces cerevisiae SIR2 gene can function in place of S. pombe sir2+, suggesting overlapping deacetylation substrates in both species. These results also suggest that, despite differences in most of the other molecules required, the two distantly related yeast species share a mechanism for targeting Sir2p homologs to silent chromatin.
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