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Reference: Darst RP, et al. (2008) Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol 28(4):1361-72

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Abstract


The broadly conserved Sir2 NAD(+)-dependent deacetylase is required for chromatin silencing. Here we report the discovery of physical and functional links between Sir2 and Slx5 (Hex3), a RING domain protein and subunit of the Slx5/8 complex, which is a ubiquitin E3 ligase that targets sumoylated proteins. Slx5 interacted with Sir2 by two-hybrid and GST-binding assays, and was found to promote silencing of genes at telomeric or rDNA loci. However, deletion of SLX5 had no detectable effect on distribution of silent chromatin components, and only slightly altered deacetylation of histone H4 lysine 16 at the telomere. In vivo assays indicated that Sir2-dependent silencing was functionally intact in the absence of Slx5. Although no previous reports suggest that Sir2 contributes to fitness of yeast populations, we found that Sir2 was required for maximal growth in slx5Delta mutant cells. A similar requirement was observed for mutants of the SUMO isopeptidase, Ulp2/Smt4. The contribution of Sir2 to optimal growth was not due to known Sir2 roles in mating-type determination or rDNA maintenance, but was connected to a role of sumoylation in transcriptional silencing. These results indicate that Sir2 and Slx5 jointly contribute to transcriptional silencing and robust cellular growth.

Reference Type
Journal Article
Authors
Darst RP, Garcia SN, Koch MR, Pillus L
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