Splitomicin is a cell-permeable lactone that acts as a selective inhibitor of NAD+ dependent histone deacetylase activity of Sir2 protein. It creates a conditional phenocopy of a sir2 deletion mutant in S. cerevisiae and sensitizes mammalian cells to a variety of DNA-damaging agents by abrogating Sir2p activity on p53. Acts by either altering or blocking access to the acetylated histone binding pocket.
