Overview:

SIRT6 is a member of the sirtuin family of proteins which are homologs to the yeast Sir2 protein. Sirtuin family contain a sirtuin core domain and are grouped into four classes with SIRT6 being a member of class IV. Human SIRT6 protein is a NAD(+)-dependent histone H3 lysine-9 deacetylase that modulates telomeric chromatin (1). SIRT6 associates specifically with telomeres and SIRT6 depletion leads to telomere dysfunction with end-to-end chromosomal fusions and premature cellular senescence. SIRT6 -/- mouse cells show that SIRT6 promotes resistance to DNA damage and suppresses genomic instability in association with a role in base excision repair (2).

References:

1. Michishita, E. et al: SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452: 492-496, 2008.

2. Mostoslavsky, R. et al: Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124: 315-329, 2006.