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Structural highlights

Function

SIR2_YEAST NAD-dependent deacetylase, which participates in a wide range of cellular events including chromosome silencing, chromosome segregation, DNA recombination and the determination of life span. Involved in transcriptional repression of the silent mating-type loci HML and HMR and telomeric silencing via its association with SIR3 and SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its association with the RENT complex, preventing hyperrecombination, and repressing transcription from foreign promoters, which contributes to extending life span. Probably represses transcription via the formation of heterochromatin structure, which involves the compaction of chromatin fiber into a more condensed form, although this complex in at least one case can still bind euchromatic levels of positive transcription regulators. Although it displays some NAD-dependent histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone H4K16Ac in vitro, such activity is unclear in vivo and may not be essential.^{[1] [2] [3] [4] [5] [6] [7]}

See Also

• Histone deacetylase 3D structures

References

1. ↑ Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell. 1999 Dec 23;99(7):735-45. PMID:10619427
2. ↑ Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. PMID:10693811 doi:http://dx.doi.org/10.1038/35001622
3. ↑ Tsukamoto Y, Kato J, Ikeda H. Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature. 1997 Aug 28;388(6645):900-3. PMID:9278054 doi:http://dx.doi.org/10.1038/42288
4. ↑ Huang J, Moazed D. Association of the RENT complex with nontranscribed and coding regions of rDNA and a regional requirement for the replication fork block protein Fob1 in rDNA silencing. Genes Dev. 2003 Sep 1;17(17):2162-76. Epub 2003 Aug 15. PMID:12923057 doi:http://dx.doi.org/10.1101/gad.1108403
5. ↑ Borra MT, Langer MR, Slama JT, Denu JM. Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. Biochemistry. 2004 Aug 3;43(30):9877-87. PMID:15274642 doi:http://dx.doi.org/10.1021/bi049592e
6. ↑ Darst RP, Garcia SN, Koch MR, Pillus L. Slx5 promotes transcriptional silencing and is required for robust growth in the absence of Sir2. Mol Cell Biol. 2008 Feb;28(4):1361-72. Epub 2007 Dec 17. PMID:18086879 doi:http://dx.doi.org/MCB.01291-07
7. ↑ Du J, Jiang H, Lin H. Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD. Biochemistry. 2009 Apr 7;48(13):2878-90. doi: 10.1021/bi802093g. PMID:19220062 doi:10.1021/bi802093g