NAD-dependent protein deacylase sirtuin-6 (SIRT6)

**NAD-dependent protein deacylase sirtuin-6 (SIRT6)** is an evolutionarily conserved enzyme belonging to the sirtuin family, characterized by its dependence on NAD(^+) as a cofactor for catalysis[1][2][4]. SIRT6 acts primarily as a histone deacetylase, most notably removing acetyl groups from histones H3 and H4, thereby regulating chromatin structure and gene expression[4][2]. It also possesses mono-ADP-ribosyltransferase activity, participating in the repair of DNA double-strand breaks by recruiting repair proteins and modulating poly(ADP-ribose) polymerase (PARP1) activity[3][4]. SIRT6 is crucial for cellular responses to genotoxic stress, genomic stability, DNA repair capacity, metabolic homeostasis, and lifespan regulation[3][4][5]. It interacts with small molecule modulators such as quercetin and cyanidin, which can activate or inhibit specific enzymatic activities[5][4]. SIRT6's functions make it a target of interest in cancer, metabolic, neurodegenerative, and aging-associated diseases, though broad sirtuin inhibition may threaten genomic integrity and cellular homeostasis[4][5].

Other names

Sirtuin 6SIRT6Sirt6NAD-dependent protein deacetylase sirtuin-6

Activation of SIRT6 deacetylation by allosteric modulation (e.g., by quercetin, cyanidin, SP-624) - Stimulation or inhibition of deacetylation and deacylation activities - Modulation of mono-ADP-ribosylation