PARP and DNA repair
PARP is a key signaling enzyme involved in triggering the repair of single-strand DNA damage.1-3
PARP-1 acts to detect and signal the presence of DNA single-stranded breaks (SSBs). Following the binding to sites of DNA damage, PARP-1 catalyses the cleavage of NAD+ into nicotinamide and ADP-ribose to produce highly charged branched chains of poly-ADP ribose that serve to recruit other repair enzymes and initiate repair of the damage.
PARP inhibition has been demonstrated to selectively kill tumor cells lacking components of the homologous recombination (HR) DNA repair pathway while sparing normal cells. Known defects in HR repair include the well-characterized hereditary BRCA1 and BRCA2 mutations in breast and ovarian cancer, as well as nonhereditary BRCA mutations.
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