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

The Poly (ADP-ribose) polymerase (PARP) family consists of 17 enzymes that are essential regulators of genomic stability, DNA repair, and programmed cell death [1, 5, 6]. These enzymes catalyze the transfer of ADP-ribose from NAD+ to target proteins, a post-translational modification known as ADP-ribosylation that signals the presence of DNA damage [1, 10, 11]. PARP1 and PARP2 are the most extensively studied members and serve as the primary targets for a class of drugs known as PARP inhibitors [4, 13, 15]. These inhibitors are particularly effective in treating cancers with homologous recombination deficiency (HRD), such as those harboring BRCA1 or BRCA2 mutations, through a mechanism called synthetic lethality [2, 7, 14]. By blocking PARP activity and trapping the enzyme on DNA, these drugs cause the accumulation of double-strand breaks that HR-deficient cancer cells cannot repair, leading to selective cell death [14, 16, 17]. Beyond oncology, the PARP family is involved in various pathological processes, including inflammation, neurodegeneration, and viral infections, making it a significant focus for diverse therapeutic applications [1, 6, 16].

Other names

Poly (ADP-ribose) polymeraseARTD familyADP-ribosyltransferase diphtheria toxin-like familyPARP superfamily

PARP inhibitors primarily act through catalytic inhibition of the PARP enzyme and PARP trapping, which stabilizes the enzyme on damaged DNA to prevent repair [14, 15, 16]. This induces synthetic lethality in cells with homologous recombination deficiency (HRD), such as those with BRCA1/2 mutations, by preventing the repair of DNA single-strand breaks and converting them into lethal double-strand breaks [4, 14, 17].