NAD-dependent histone deacetylase SIR2 (Sir2p) (Sir2p)

Yeast Sir2p (Silent Information Regulator 2) is the founding member of the sirtuin family of NAD+-dependent protein deacetylases (UniProt [1]). It is primarily known for its role in gene silencing at the silent mating-type loci, telomeres, and ribosomal DNA (rDNA) in Saccharomyces cerevisiae (PMC [6]). By deacetylating lysine residues on histones, particularly H4K16, Sir2p promotes the formation of repressive heterochromatin and suppresses unequal recombination within the rDNA repeats (PMC [7]). This suppression of recombination is a major factor in determining the replicative lifespan of yeast cells, as it prevents the formation of toxic extrachromosomal rDNA circles (PubMed [12]). Sir2p also acts as a metabolic sensor, linking the availability of NAD+ to the regulation of aging and stress responses, particularly during calorie restriction (PMC [14]). In addition to its role in yeast biology, Sir2p serves as a critical model for understanding human sirtuins like SIRT1, which are implicated in age-related diseases and cancer (PMC [13]). Small molecules such as resveratrol have been identified as activators of Sir2p, while compounds like splitomicin and nicotinamide act as potent inhibitors (PMC [8], PMC [9]). Research into Sir2p continues to provide insights into the epigenetic mechanisms of longevity and the potential for therapeutic intervention in metabolic and degenerative disorders (NCBI [10]).

Other names

Silent information regulator 2Regulatory protein SIR2Sirtuin 2MAR1

NAD+-dependent deacetylation of lysine residues on histones and other proteins, coupled with the hydrolysis of NAD+ to produce nicotinamide and O-acetyl-ADP-ribose (UniProt [1], PMC [7]).