Poly(ADP-ribose) polymerase (PARP)

Poly(ADP-ribose) polymerase comprises a family of 17 enzymes, with PARP1 being the most extensively studied. These nuclear enzymes detect DNA damage—particularly single-strand breaks—and stimulate DNA repair processes by catalyzing the addition of ADP-ribose units from NAD+ to various protein substrates, forming poly(ADP-ribose) chains that serve as signals to recruit the DNA repair machinery[1][2][3][4]. PARPs also regulate transcription, chromatin structure, and cell death pathways. Overactivation of PARP may deplete NAD+ and ATP, leading to energy crisis and necrotic cell death. PARP inhibitors, especially those selective for PARP1/2, have become important treatments for cancers with impaired homologous recombination, such as BRCA1/2 mutations, by inducing synthetic lethality and tumor cell death[3]. While generally considered enzymes, certain family members (Tankyrases) additionally regulate telomere maintenance and Wnt signaling[2].\nPoly(ADP-ribose) polymerase is a well-characterized therapeutic target with extensive molecular, biological, and clinical data available[1][2][3][4].

Other names

PARPPoly(ADP-ribose) synthetaseADP-ribosyltransferase diphtheria toxin-like (ARTD) enzymeTankyrase (for specific PARP-5a/PARP-5b family members)

Inhibition of DNA repair by blocking PARP catalytic activity, leading to accumulation of DNA damage and cell death (synthetic lethality, notably in cells deficient for homologous recombination repair such as BRCA1/2 mutant cells); Activation (less common) boosts DNA repair.