Poly [ADP-ribose] polymerase 1, 2, and 3 (PARP-1/2/3)

Poly [ADP-ribose] polymerase 1, 2, and 3 (PARP-1/2/3) are nuclear enzymes that serve as critical sensors and mediators of the cellular DNA damage response [7, 12]. PARP-1 is the most abundant and active member, responsible for the majority of cellular poly(ADP-ribosyl)ation (PARylation), a post-translational modification where ADP-ribose units from NAD+ are transferred onto target proteins to facilitate the recruitment of DNA repair machinery [8, 17]. PARP-2 and PARP-3 also contribute to DNA repair pathways, with PARP-3 specifically implicated in the repair of double-strand breaks and the regulation of PARP-1 activity [8, 14]. In oncology, these enzymes are the primary targets of PARP inhibitors, which exploit the principle of synthetic lethality in tumors with defective homologous recombination, such as those harboring BRCA1 or BRCA2 mutations [1, 3, 4]. By inhibiting the enzymatic activity and trapping PARP proteins on DNA, these drugs cause the collapse of replication forks and the accumulation of lethal DNA damage in cancer cells [1, 2, 11]. Beyond their role in DNA repair, PARP-1/2/3 are involved in transcriptional regulation, chromatin remodeling, and cell death pathways, making them significant targets in cancer, inflammation, and neurodegenerative diseases [7, 9, 17].

Other names

PARP1PARP2PARP3ARTD1ARTD2ARTD3Poly(ADP-ribose) synthetaseADPRTADPRTL1ADPRTL2ADPRTL3PPOL

Competitive inhibition of the PARP catalytic domain (competing with NAD+) and PARP trapping on DNA, leading to the accumulation of unrepaired DNA breaks and synthetic lethality in homologous recombination-deficient cells [1, 2, 3, 11].