SIRT6 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. Sirt6 is mainly known as a deacetylase of histones H3 and H4, an activity by which it changes chromatin density and regulates gene expression. The enzymatic activity of Sirt6, as well as of the other members of the sirtuins family, is dependent upon the binding of the cofactor nicotinamide adenine dinucleotide (NAD+). SIRT6 is a chromatin-associated protein that is required for normal base excision repair and double-strand break repair of DNA damage in mammalian cells. SIRT6 promotes the repair of DNA double-strand breaks by the process of non-homologous end joining and homologous recombination. SIRT6 stabilizes the repair protein DNA-PKcs (DNA-dependent protein kinase catalytic subunit) at chromatin sites of damage.
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