Poly(ADP-ribose) polymerase 1 (PARP1) and Poly(ADP-ribose) polymerase 2 (PARP2) (PARP1 and PARP2)

Poly(ADP-ribose) polymerase 1 (PARP1) and Poly(ADP-ribose) polymerase 2 (PARP2) are nuclear enzymes that catalyze the transfer of ADP-ribose units from NAD+ to target proteins, forming poly-ADP-ribose chains in a process called PARylation. This modification is critical for DNA repair, notably base excision repair and single-strand break repair, and for maintenance of genome stability. PARP1 accounts for around 90% of PARP activity, while PARP2 contributes 10-15%. Both enzymes are structurally homologous in their catalytic domains but differ in other domains, impacting substrate interaction and activity. Clinically, inhibition of PARP activity, especially in tumors with defective homologous recombination (e.g., BRCA-mutated cancers), induces cell death and is a validated therapeutic strategy. Several PARP inhibitors are approved for cancer treatment. However, the name "PARP1/2 polymerase 1/2)" is not standardized, and it is recommended to refer to each enzyme separately for molecular targeting purposes

Other names

PARP1PARP2ADP-ribosyltransferase diphtheria toxin-like 1 (for PARP1)ADP-ribosyltransferase diphtheria toxin-like 2 (for PARP2)Poly(ADP-ribose) synthase 1/2ARTD1 (PARP1)ARTD2 (PARP2)

Inhibition of PARP enzymatic activity blocks DNA repair, leading to synthetic lethality especially in cells with defects in homologous recombination (e.g., BRCA1/2 mutant cancer cells) Prevention of poly-ADP-ribose polymer formation, stalling DNA repair and promoting cell death in malignant cells