Sirtuin-dependent epigenetic regulation in the maintenance of genome integrity

Abstract

Sirtuins are a family of deacetylases that target histone and non-histone proteins and require NAD(+) as an enzymatic cofactor for their enzymatic activity. This requirement confers sirtuins with the ability to detect changes in metabolism and energy homeostasis and to coordinate cellular responses to maintain genome integrity. Thus, sirtuins are crucial in the crosstalk between environment and genome, and therefore in responses to stress at the cell and organism levels. Sirtuins play a major role in maintaining genome integrity, largely through regulation of epigenetic mechanisms. They target different histone marks, including H4K16Ac, H3K9Ac, H3K56Ac and H3K18Ac, and non-histone components of the chromatin machinery, such as enzymes and structural proteins. Here we summarize our current view on the link between sirtuins and epigenetics, one that reflects the continual adaptation of the genome to stress.

Keywords: HAT; HDAC; HMT; chromatin regulation; constitutive heterochromatin; epigenetics; facultative heterochromatin; genome stability; histone acetylation; sirtuins.