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Sir2 is a nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylase involved in gene silencing and longevity. Cellular stresses affect Sir2 activity, but the mechanisms of Sir2 regulation are debated. Nicotinamide has been proposed as a physiological regulator that inhibits Sir2 deacetylase activity by chemical reversal of a covalent reaction intermediate. We demonstrate a chemical...
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