Poly [ADP-ribose] polymerase 1 and Poly [ADP-ribose] polymerase 2 (PARP1 (for Poly [ADP-ribose] polymerase 1), PARP2 (for Poly [ADP-ribose] polymerase 2))

Poly [ADP-ribose] polymerase 1 (PARP1) and Poly [ADP-ribose] polymerase 2 (PARP2) are closely related nuclear enzymes involved in the detection of DNA strand breaks and the initiation of DNA repair through poly(ADP-ribosyl)ation, using NAD+ to synthesize poly(ADP-ribose) chains[4][5][6]. They contribute to genome stability by facilitating repair of single-strand and double-strand DNA breaks—PARP1 is more abundant (about 90% of nuclear PARP activity) and interacts with DNA via zinc finger domains, while PARP2 is activated mainly by DNA containing 5'-phosphates and interacts via its WGR domain[2][5][1]. Both enzymes play overlapping and specific roles in base excision repair, chromatin remodeling, and cell death regulation[2][5][4]. Inhibition of PARP activity is therapeutically exploited, particularly in cancers with defects in homologous recombination repair (such as BRCA-mutated tumors), leading to synthetic lethality[6][4]. Adverse events associated with PARP inhibition include hematological toxicity and gastrointestinal effects. Therapeutic efficacy is linked to specific genomic biomarkers, most notably BRCA1/2 mutation status[4][6].

Other names

PARP-1PARP-2ADPRT (for ADP-ribosyltransferase)ARTD1 and ARTD2 (alternate designations)

Inhibition of PARP enzymatic activity at the NAD+ binding site; Induction of synthetic lethality in BRCA1/2-deficient cancer cells; Disruption of DNA repair, leading to accumulation of DNA damage