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

Poly [ADP-ribose] polymerase 1 (PARP1) and Poly [ADP-ribose] polymerase 2 (PARP2) are enzymes primarily involved in the detection and repair of single-strand DNA breaks through the base excision repair pathway. Upon binding to damaged DNA, they catalyze the transfer of ADP-ribose units from NAD\(^+\) to target proteins (including themselves), producing poly(ADP-ribose) chains that serve as signals to recruit and assemble DNA repair complexes. PARP1 accounts for the majority of PARP activity in cells, while PARP2 contributes to a lesser extent but fulfills complementary and overlapping roles, including chromatin regulation and maintenance of genome stability. Inhibition of these proteins is a validated therapeutic strategy in cancers with defects in homologous recombination repair, such as those carrying BRCA1/2 mutations.

Other names

ADPRTPARPPoly (ADP-ribose) synthetase 1ADPRT2Poly (ADP-ribose) synthetase 2

Inhibition of PARP1/2 enzymatic activity leads to accumulation of DNA damage in cancer cells deficient in homologous recombination repair (synthetic lethality). Blocking poly(ADP-ribosyl)ation prevents recruitment of DNA repair proteins, resulting in cell death, particularly in BRCA-mutant or other HR-deficient cancers.