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

Poly [ADP-ribose] polymerase 3 (PARP-3) is a member of the PARP enzyme family that primarily functions as a mono-ADP-ribosyltransferase, catalyzing the transfer of a single ADP-ribose unit from NAD+ onto target proteins such as histones and DNA repair factors [2, 3]. Unlike PARP-1 and PARP-2, which generate long poly(ADP-ribose) chains, PARP-3 plays a specialized role in the cellular response to DNA double-strand breaks by facilitating the non-homologous end joining (NHEJ) repair pathway and regulating mitotic spindle stability and centrosome function [1, 18]. In oncology, PARP-3 is frequently overexpressed in aggressive malignancies, including triple-negative breast and ovarian cancers, where it promotes epithelial-mesenchymal transition (EMT) and contributes to chemoresistance [2, 20]. While most clinically approved PARP inhibitors were originally developed to target PARP-1 and PARP-2, they often exhibit cross-reactivity with PARP-3, which may contribute to their overall therapeutic efficacy in homologous recombination-deficient tumors [10, 14]. Selective PARP-3 inhibitors are currently being investigated as potential tools to enhance the precision of DNA damage-targeted therapies while minimizing off-target toxicities [2, 14].

Other names

PARP3ADPRT3ADPRTL2ADPRTL3ARTD3IRT1pADPRT-3ADP-ribosyltransferase diphtheria toxin-like 3

Inhibition of mono-ADP-ribosyltransferase activity, disruption of non-homologous end joining (NHEJ) DNA repair pathways, and induction of synthetic lethality in homologous recombination-deficient cells.