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A more recent version of this article appeared on April 1, 2002
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Submitted on October 5, 2001
Revised on December 12, 2001
Accepted on January 4, 2002
1 Department of Biology, Massachusetts Institute of Technology,
Cambridge, MA 02139
2 Department of Biology, Massachusetts Institute of Technology, Building 68-280A, 77 Massachussetts Ave., Cambridge, MA 02139
* Corresponding author. E-mail address: leng{at}mit.edu.
The yeast SIR2 gene and many of its homologues have been identified as NAD+ dependent histone deacetylases. To get a broader view of the relationship between the histone deacetylase activity of Sir2p and its in vivo functions we have mutated 8 highly conserved residues in the core domain of SIR2. These mutations have a range of effects on the ability of Sir2p to deacetylate histones in vitro and to silence genes at the telomeres and HM loci. Interestingly, there is not a direct correlation between the in vitro and in vivo effects in some of these mutations. We also show that the histone deacetylase activity of Sir2p is necessary for the proper localization of the SIR complex to the telomeres.
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