Enzymatic activities of Sir2 and chromatin silencing

Heritable domains of generalized repression are a common feature of eukaryotic chromosomes and involve the assembly of DNA into a silenced chromatin structure. Sir2, a conserved protein required for silencing in yeast, has recently been shown to couple histone deacetylation to cleavage of a high-energy bond in nicotinamide adenine dinucleotide (NAD) and the synthesis of a novel product, O-acetyl-ADP-ribose. The deacetylase activity provides a direct link between Sir2 and the hypoacetylated state of silent chromatin. However, the unusual coupling of deacetylation to cleavage and synthesis of other bonds raises the possibility that deacetylation is not the only crucial function of Sir2.