Poly(ADP-ribose) polymerase 1, 2, and 3 (PARP1, PARP2, PARP3)

Poly(ADP-ribose) polymerases 1, 2, and 3 (PARP1, PARP2, PARP3) are closely related nuclear enzymes that play essential roles in cellular DNA damage detection and repair, especially in pathways such as base excision repair and non-homologous end joining. PARP1, the best-studied, detects DNA strand breaks and catalyzes the addition of ADP-ribose polymers to target proteins and itself (PARylation) using NAD(+) as a substrate, signaling and recruiting DNA repair machinery. PARP2 and PARP3 have distinct, though overlapping, roles in DNA repair and exhibit differences in activation and substrate specificity. Inhibition of these enzymes, especially PARP1 and PARP2, is therapeutically exploited in cancer, taking advantage of synthetic lethality in DNA repair-deficient cells, particularly those with BRCA mutations. Their activity also regulates cell death pathways, chromatin remodeling, and transcription, with dysregulation implicated in cancer, neurodegeneration, and inflammatory diseases.

Other names

PARP-1, ADPRT, ARTD1 (for PARP1)PARP-2, ADPRT2, ARTD2 (for PARP2)PARP-3, ADPRT3, ARTD3 (for PARP3)Poly ADP-ribose polymerase (collectively)DNA-dependent ADP-ribosyltransferases (collectively)

Inhibition of catalytic activity (compete with NAD(+) at the active site); "Trapping" of PARP enzymes on damaged DNA, blocking DNA repair; Induction of synthetic lethality in cells with deficient homologous recombination repair, e.g., BRCA-mutated cancers