Poly(ADP-ribose) polymerase (PARP) (PARP)

The Poly(ADP-ribose) polymerase (PARP) family, including members PARP-1, PARP-2, PARP-3, PARP-4, PARP-10, PARP-12, PARP-15, and PARP-16, consists of enzymes that catalyze the transfer of ADP-ribose units from NAD+ onto target proteins (UniProt, 2024). PARP-1, PARP-2, and PARP-3 are critical sensors of DNA damage, particularly single-strand breaks, and are essential for the base excision repair pathway (PubMed, PMID: 32803710). Other members like PARP-10 and PARP-12 function as mono-ADP-ribosyltransferases involved in antiviral responses and metabolic signaling, while PARP-16 plays a role in the endoplasmic reticulum stress response (NCBI, 2023; PubMed, PMID: 21555454). In oncology, PARP inhibitors exploit the concept of synthetic lethality, where inhibiting PARP in cells already deficient in homologous recombination (e.g., BRCA1/2 mutations) leads to catastrophic DNA damage and cell death (Nature Reviews Cancer, 2021). These drugs work by both blocking the enzyme's catalytic activity and by trapping the PARP protein on DNA, which prevents the progression of replication forks (Cancer Discovery, 2012). Clinically, PARP inhibitors are standard of care for several cancers, though therapeutic use is often limited by hematologic toxicities and the potential for developing secondary malignancies (FDA, 2023; StatPearls, 2023).

Other names

ARTD familyADP-ribosyltransferase diphtheria toxin-likePoly(ADP-ribose) synthetaseNAD(+) ADP-ribosyltransferasePARP-1/2/3/4/10/12/15/16

Inhibition of poly(ADP-ribose) polymerase catalytic activity and the trapping of PARP enzymes on damaged DNA, leading to the collapse of replication forks and double-strand breaks.