Markers of Poly (ADP-Ribose) Polymerase Activity as Correlates of DNA Damage

Poly (ADP-ribose) polymerase (PARP-1; EC 2.4.2.30) is a predominantly nuclear enzyme long presumed to function in the identification and repair of DNA strand nicks and breaks (for recent reviews see: 1 –3 ). PARP is comprised of a N-terminal DNA-binding domain, a central automodification domain (site of auto poly-ADP-ribosylation), and a C-terminal catalytic domain. In its traditional role, PARP-1 is believed to be activated following single or double strand DNA breakage induced by a variety of stressors such as UV radiation, and oxidative stressors such as hydrogen peroxide, and the superoxide, hyroxyl, and peroxynitrite free radicals (4 –6 ). In response, PARP is known to polyribosylate itself and a variety of other (predominantly nuclear) proteins. Nicotinamide adenine dinucleotide (NAD⁺ ) is the substrate for the reaction, and intracellular stores of NAD⁺ are consumed as the polymers of ADP-ribose (PAR) are formed by activated PARP (7 ).