Poly [ADP-ribose] polymerase 1 and 2 (PARP1/2)

Poly [ADP-ribose] polymerase 1 and 2 (PARP1 and PARP2) are essential nuclear enzymes that act as sensors for DNA damage, particularly single-strand breaks. Upon detecting a lesion, they utilize nicotinamide adenine dinucleotide (NAD+) to synthesize and attach poly(ADP-ribose) (PAR) chains to themselves and other proteins, a process known as PARylation that recruits the DNA repair machinery. This function is critical for maintaining genomic integrity and regulating cellular processes such as transcription and chromatin remodeling. In oncology, PARP1 and PARP2 are primary targets for a class of drugs known as PARP inhibitors, which exploit the principle of synthetic lethality in tumors with existing DNA repair defects, such as BRCA1 or BRCA2 mutations. These inhibitors work by blocking the catalytic activity of the enzymes and trapping them on DNA, leading to the accumulation of double-strand breaks that the cancer cell cannot repair, ultimately resulting in cell death. Beyond cancer, the role of PARP in inflammation and metabolic regulation makes it a subject of interest for treating neurodegenerative and cardiovascular diseases.

Other names

PARPADPRTARTD1ARTD2Poly(ADP-ribose) synthetaseNAD+ ADP-ribosyltransferase

PARP catalytic inhibition, PARP trapping, and induction of synthetic lethality in HR-deficient cells