Silent information regulator 2 (Sir2) proteins, or sirtuins, are protein deacetylases dependent on nicotine adenine dinucleotide (NAD) and are found in organisms ranging from bacteria to humans. In eukaryotes, sirtuins regulate transcriptional repression, recombination, the celldivision cycle, microtubule organization, and cellular responses to DNA-damaging agents. Sirtuins have also been implicated in regulating the molecular mechanisms of aging. The Sir2 catalytic domain, | Protein family review Sirtuins Sir2-related NAD-dependent protein deacetylases Brian J North and Eric Verdin Address Gladstone Institute of Virology and Immunology University of California San Francisco CA 94141 USA. Correspondence Eric Verdin. E-mail everdin@ Published 28 April 2004 Genome Biology 2004 5 224 The electronic version of this article is the complete one and can be found online at http 2004 5 5 224 2004 BioMed Central Ltd Summary Silent information regulator 2 Sir2 proteins or sirtuins are protein deacetylases dependent on nicotine adenine dinucleotide NAD and are found in organisms ranging from bacteria to humans. In eukaryotes sirtuins regulate transcriptional repression recombination the celldivision cycle microtubule organization and cellular responses to DNA-damaging agents. Sirtuins have also been implicated in regulating the molecular mechanisms of aging. The Sir2 catalytic domain which is shared among all sirtuins consists of two distinct domains that bind NAD and the acetyl-lysine substrate respectively. In addition to the catalytic domain eukaryotic sirtuins contain variable amino- and carboxy-terminal extensions that regulate their subcellular localizations and catalytic activity. Gene organization and evolutionary history Protein acetylation regulates a wide variety of cellular functions including the recognition of DNA by proteins proteinprotein interactions and protein stability reviewed in 1 . Post-translational modification of proteins at lysine residues by reversible acetylation is catalyzed by the opposing activities of histone acetyltransferases HATs and histone deacetylases HDACs which act on both histone and non-histone substrates despite their names. HDACs are grouped into three classes on the basis of their homology to yeast transcriptional repressors. Class I and class II HDACs which share significant similarity to each other in their catalytic cores are homologs of the yeast deacetylases .
