ABSTRACT
CHRISTIAN BLENN, PHILIPPE WYRSCH, and FELIX R. ALTHAUS
THE LIFE CYCLE OF POLY (ADP-RIBOSE)
Poly(ADP-ribosyl)-ation belongs to the nonprotein posttranslational modifications and is a metabolite of the enzymatic cofactor nicotinamide adenine dinucleotide (NAD+). Poly (ADP-ribose) polymerases (PARPs) cleave the nicotinic moiety from NAD+ and convert the ADP-ribose (ADPR) units into long APD-ribose polymers (PAR). At the protein level, the E-D-loop-E-D NAD+ fold is the most conserved region in PARPs and is therefore termed the PARP signature motif [1-3]. To date, 17 distinct PARP enzymes have been discovered and numbered accordingly. Recently a new nomenclature has been suggested that is based on their transferase activity (ARTD nomenclature [4]): PARP1 (ARTD1), PARP2 (ARTD2), PARP3 (ARTD3), PARP4 (ARTD4, vault-PARP), PARP5A (ARTD5, Tankyrase 1), PARP5B (ARTD6, Tankyrase 2), PARP6 (ARTD17), PARP7 (ARTD14, TIPARP, RM1), PARP8 (ARTD16), PARP9 (ARTD9, BAL1), PARP10 (ARTD10), PARP11 (ARTD11), PARP12 (ARTD12, ZH3HDC1), PARP13 (ARTD13, ZC3HAV1, ZAP1), PARP14 (ARTD8, BAL2 COAST6), PARP15 (ARTD7, BAL3), and PARP16 (ARTD15). However, not all PARP enzymes are proven poly(ADP-ribose) polymerases. Several of them seem to belong to the class of mono(ADP-ribosyl) transferases [5]. The nuclear PARP1 and PARP2 are the best characterized PARPs in mammals and are true poly(ADP-ribose) polymerases. PARP1 has a modular structure and starts its catalytic activity after binding to DNA nicks and breaks with the double zinc finger
domain [2]. Recently, a third zinc finger-like structure was discovered. It is required for transmitting DNA-induced conformational changes to the catalytic domain [6,7].
