Potent Activation of NAD⁺-Dependent Deacetylase Sirt7 by Nucleosome Binding.

ABSTRACT: Sirtuin-7 (Sirt7) is a nuclear NAD⁺-dependent deacetylase with a broad spectrum of biological functions. Sirt7 overexpression is linked to several pathological states and enhances anticancer drug resistance, making the enzyme a promising target for the development of novel therapeutics. Despite a plethora of reported in vivo functions, the biochemical characterization of recombinant Sirt7 remains inadequate for the development of novel drug candidates. Here, we conduct an extensive biochemical analysis of Sirt7 using newly developed binding and kinetic assays to reveal that the enzyme preferentially interacts with and is activated by nucleosomes. Sirt7 activation by nucleic acids alone is effective toward long-chain acylated hydrophobic substrates, while only nucleosome b

SUBMITTER: Kuznetsov VI 

PROVIDER: S-EPMC9499614 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature