Poly [ADP-ribose] polymerase 1 (PARP-1) (PARP-1)

Poly [ADP-ribose] polymerase 1 (PARP-1) is a nuclear enzyme that acts as a sensor for DNA damage, specifically single-strand breaks [UniProt P09874]. It catalyzes the polymerization of ADP-ribose units from NAD+ onto target proteins, a process essential for recruiting DNA repair factors like XRCC1 [PubMed: 11134486]. In cancer therapy, PARP-1 is targeted to induce synthetic lethality in tumors with homologous recombination deficiencies, such as those with BRCA1 or BRCA2 mutations [StatPearls: NBK544271]. Beyond enzymatic inhibition, many therapeutic agents work by PARP trapping, where the enzyme is locked onto DNA, preventing replication fork progression [PubMed: 23230003]. While primarily known for its role in DNA repair, PARP-1 overactivation can lead to cellular energy depletion and a specific form of cell death called parthanatos, which is implicated in neurodegeneration and ischemia [PubMed: 21451529].

Other names

PARP1ADPRTADPRT1PPOLARTD1NAD(+) ADP-ribosyltransferase 1Poly[ADP-ribose] synthase 1

Competitive inhibition of the catalytic site (NAD+ binding) and PARP trapping, where the enzyme is stabilized on DNA damage sites, leading to the collapse of replication forks and double-strand breaks [PubMed: 23230003].