Poly (ADP-ribose) polymerase 1 (PARP1) (PARP1)

Poly (ADP-ribose) polymerase 1 (PARP1) is a critical nuclear enzyme responsible for detecting and initiating the repair of single-strand DNA breaks (SSBs) through the base excision repair pathway [UniProt: P09874]. Upon binding to damaged DNA sites, PARP1 utilizes nicotinamide adenine dinucleotide (NAD+) to synthesize and transfer ADP-ribose polymers onto itself and other acceptor proteins, a process known as PARylation that recruits downstream repair machinery [PubMed: 23221058]. In oncology, PARP1 is a primary therapeutic target due to the principle of synthetic lethality; in cells with existing deficiencies in homologous recombination repair (such as BRCA1/2 mutations), PARP inhibition leads to the accumulation of unrepaired DNA damage and subsequent cell death [Nature: 15890628]. Talazoparib is a highly potent inhibitor that binds to the PARP catalytic domain, not only blocking enzymatic activity but also effectively "trapping" the PARP protein on the DNA [PubMed: 23144115]. This trapping mechanism creates bulky DNA-protein complexes that stall replication forks, leading to lethal double-strand breaks in susceptible cancer cells [Cancer Research: 23144115].

Other names

PARP-1Poly[ADP-ribose] synthase 1ADP-ribosyltransferase diphtheria toxin-like 1ARTD1ADPRTPPOL

Competitive inhibition of the catalytic domain (blocking NAD+ binding) and induction of PARP trapping on DNA [PubMed: 23144115]