| dc.description.abstract | Lysine acylation serves as an epigenetic marker for myriad cellular processes, such as signaling, differentiation, DNA repair, angiogenesis, and the like. Sirtuin 1 (SIRT1) and Sirtuin 2 (SIRT2) are NAD+ -dependent histone deacylases that operate as posttranslational regulators of lysine acylation states. Despite being a topic of increasing interest, little effort has been made to completely understand the overall character of these two sirtuin enzymes. Most of the studies have also been on the peptide level and not on actual sirtuin substrates (i.e. histone H3/H4 tetramers and nucleosomes). Thus the demand for systematic studies of enzymatic activities on native substrates for SIRT1 and SIRT2 is currently needed.
In this dissertation, we discuss the ability for SIRT1 and SIRT2 to deacylate various short-chain acylations—acetylation, crotonylation, and butyrylation—from lysine residues on the tetramer and nucleosome substrates. In addition, we explore the difference in selectivity between using peptide and nucleosome substrates with sirtuins. We find that SIRT1 and SIRT2 demonstrate relatively no substrate specificity across the screened histone H3 sites, contrary to previous expectations.
The implication of the overall non-specificity of SIRT1 and SIRT2 on the tetramer and nucleosome substrates suggests that these sirtuin enzymes have an adaptive nature, harnessing an ability to respond to various cellular situations, rather than an enzyme specifically designed for a particular task or function. | en |
