The silent information regulator (SIR2) family of genes are highly conserved from prokaryotes to eukaryotes and are involved in diverse processes, including transcriptional regulation, cell cycle progression, DNA-damage repair and aging. In S. cerevisiae, Sir2p deacetylates histones in a NAD-dependent manner, which regulates silencing at the telomeric, rDNA and silent mating-type loci. Sir2p is the founding member of a large family, designated sirtuins, which contain a conserved catalytic domain. The human homologs, which include SIRT1-7, are divided into four main branches: SIRT1-3 are class I, SIRT4 is class II, SIRT5 is class III and SIRT6-7 are class IV. SIRT proteins may function via mono-ADP-ribosylation of proteins. SIRT2 contains a 323 amino acid catalytic core domain with a NAD-binding domain and a large groove which is the likely site of catalysis.