Fig. 2

Mechanism of Action of PARP Inhibitors. Note: in the presence of a PARP inhibitor, PARP1 is activated by DNA damage (single strand break). BER is blocked and, on replication, a DSB is formed from the single strand break. In presence of functional If HRR (in normal healthy cells), DNA damage is repaired, and the cell survives. In cells with HRR deficiency (as seen in BRCA mutations), the break is either not repaired or repaired by error-prone NHEJ or MMEJ. This causes genomic instability and ultimately cell death. Footnote: BER: Base excision repair; BRCA: breast and ovarian cancer susceptibility gene; DSB: DNA double-strand breaks; HRD: HRR deficiency; HRR: homologous recombination repair; MMEJ: microhomology-mediated end-joining; NHEJ: nonhomologous end-joining; PARP: poly (ADP-ribose) polymerase