PARP

Notes

original target text: PARP inhibitor

PARP (poly-ADP-ribose polymerase) refers to a family of enzymes, most notably PARP1, that detect and help repair single-strand breaks in DNA. When such breaks occur, PARP binds to them and adds chains of ADP-ribose units, recruiting additional repair proteins to the site. This activity is one of several DNA repair pathways that cells rely on to maintain genomic integrity. PARP inhibitors block this enzymatic activity and also trap PARP protein onto damaged DNA, preventing normal repair and allowing breaks to persist or convert into more dangerous double-strand breaks during cell division. Healthy cells with intact backup repair pathways, particularly homologous recombination, can often tolerate this loss, but cells that already carry defects in homologous recombination repair (as occurs with certain inherited or acquired mutations) become overwhelmed by unrepaired DNA damage and die. This concept, known as synthetic lethality, underlies the therapeutic rationale for PARP inhibition in cancers with homologous recombination deficiency. Because the mechanism selectively exploits an existing repair vulnerability rather than broadly poisoning all dividing cells, it represents a targeted approach to inducing cancer cell death while sparing many normal tissues, though it is not entirely free of effects on healthy cells that also depend on DNA repair capacity.