DNA damage, sirtuins, and epigenetic marks

Sirtuins are class III NAD+-dependent histone deacetylases (HDACs), able to modify several proteins, including histones. Due to their deacetylase activity in histones, they are involved with important epigenetic modifications. Sirtuins mediate a wide range of biological functions, including an essential role in cellular adaptation to stress by the modulation of DNA damage response and repair and the regulation of chromatin integrity and gene expression. Sirtuins may recruit and activate many DNA repair factors to damaged sites, facilitating DNA damage response. Besides that, the recruitment and activation of histone acetyltransferases (HATs) and methyltransferases (HMTs) make sirtuins crucial in regulating heterochromatin formation and gene silencing. Sirtuins seem to be a major epigenetic regulator of transcriptional profile and genomic stability, well-known hallmarks of cancer. Here, we will discuss how sirtuins can impact the DNA damage or repair mechanisms by modifying or inducing epigenetic modifications, such as chromatin remodeling, histone acetylation, and methylation.