Poly(ADP-ribose) polymerase 1 & 2 (PARP1/2)

Poly(ADP-ribose) polymerase 1 (PARP1) and Poly(ADP-ribose) polymerase 2 (PARP2) are nuclear enzymes belonging to the ADP-ribosyltransferase family. Both catalyze the poly(ADP-ribosyl)ation (PARylation) of target proteins using NAD+ as a substrate, primarily in response to DNA damage. While PARP1 accounts for the majority of nuclear PARylation activity and binds sites of DNA single- and double-strand breaks, PARP2, a closely related homolog, also plays an essential role in DNA repair, chromatin modulation, and cell death regulation, often cooperating with PARP1. Both enzymes are crucial for facilitating DNA repair through mechanisms like recruitment of repair factors and chromatin remodeling, thereby maintaining genomic stability. The combined loss or inhibition of PARP1 and PARP2 can lead to profound genomic instability and is embryonic lethal. Therapeutic inhibition of PARP1 and PARP2 is clinically established in cancer, particularly in tumors with deficient homologous recombination DNA repair (e.g., BRCA mutation), representing a key strategy in oncology.

Other names

Poly [ADP-ribose] polymerase 1Poly [ADP-ribose] polymerase 2PARP-1PARP-2ADPRTADPRTL1PARP

Inhibition of catalytic activity (blocks PAR chain synthesis, impairs DNA repair, leading to synthetic lethality in homologous recombination-deficient cancers, e.g., BRCA1/2-mutant tumors); Trapping of PARP-DNA complexes