Genetics. Published Articles Ahead of Print: June 18, 2006, Copyright © 2006
doi:10.1534/genetics.106.055491


A more recent version of this article appeared on August 1, 2006.


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New alleles of SIR2 define cell cycle specific silencing functions

1 University of Virginia
2 Wesleyan University
3 National Institutes of Health
4 Rockefeller University
5 Harvard Medical School

* To whom correspondence should be addressed. E-mail: sholmes{at}wesleyan.edu.

Submitted on January 5, 2006
Revised on March 4, 2006
Accepted on 1 June 2006


Abstract

The establishment of transcriptional silencing in yeast requires cell cycle progression, but the nature of this requirement is unknown. Sir2 is a protein deacetylase that is required for gene silencing in yeast. We have used temperature sensitive alleles of the SIR2 gene to assess Sir2's contribution to silencing as a function of the cell cycle. When examined in vivo these conditional alleles fall into two classes: one class exhibits a loss of silencing when raised to the non-permissive temperature regardless of cell cycle position, while the second class exhibits a mitosis-specific silencing defect. Alleles of the first class have a primary defect in protein deacetylase activity, while the class two alleles are specifically defective in Sir2-Sir4 interactions at non-permissive temperatures. Using a SIR2 temperature sensitive allele we show that silencing can be established at the HML locus during progression through the G2/M to G1 interval. These results suggest that yeast heterochromatin undergoes structural transitions as a function of the cell cycle and support the existence of a critical assembly step for silent chromatin in mitosis.

Key Words: Sir2, cell cycle, chromatin, silencing, transcription




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