Poly [ADP-ribose] polymerase 3 (PARP3) (PARP3)

Poly [ADP-ribose] polymerase 3 (PARP3) is an enzyme belonging to the PARP family that primarily functions as a mono-ADP-ribosyltransferase, catalyzing the transfer of a single ADP-ribose unit to target proteins [1, 15]. It plays a pivotal role in the DNA damage response, specifically facilitating the repair of double-strand breaks via the non-homologous end-joining (NHEJ) pathway and cooperating with PARP1 to maintain genomic stability [1, 12]. Beyond DNA repair, PARP3 is involved in regulating mitotic progression, spindle stabilization, and telomere integrity [3, 10, 16]. It also modulates gene expression through interactions with Polycomb group proteins and is involved in epithelial-mesenchymal transition (EMT) [1, 7, 8]. In clinical oncology, PARP3 is a significant therapeutic target; its inhibition is particularly effective in cancers with homologous recombination deficiencies, such as those harboring BRCA1 or BRCA2 mutations, through the mechanism of synthetic lethality [1, 4, 14]. While current FDA-approved PARP inhibitors like olaparib and rucaparib target multiple PARP isoforms including PARP3, selective PARP3 inhibitors are being explored to enhance efficacy and reduce off-target toxicities in aggressive malignancies like triple-negative breast cancer [1, 4, 9]. PARP3 overexpression has been linked to tumor aggressiveness and chemoresistance in various cancers, including glioblastoma and neuroblastoma [9, 10]. Therapeutic challenges include the potential for drug resistance and the management of hematologic toxicities associated with PARP inhibition [4, 17].

Other names

ADPRT3ADPRTL2ADPRTL3ARTD3IRT1PADPRT-3Poly(ADP-ribose) polymerase family member 3NAD(+) ADP-ribosyltransferase 3Protein mono-ADP-ribosyltransferase PARP3

PARP inhibition