fig1

Figure 1. Synthetic lethality. There is failure of DNA base excision/single-strand break repair in the presence of PARPi. This causes stalling of the replication fork and subsequently collapse, leading to double-strand breaks which are repaired by homologous recombination when this pathway is intact. In the presence of a BRCA mutation or HRD, DNA double-strand breaks are repaired by NHEJ leading to genomic instability, cell cycle arrest and apoptosis. PARP inhibition in the presence of a BRCA mutation is synthetically lethal. PARP: poly-adenosine diphosphate ribose polymerase; PARPi: poly-adenosine diphosphate ribose polymerase inhibitors; BER: base excision repair; SSB: single-strand break; NHEJ: non-homologous end joining; HRD: homologous recombination deficiency; DNA: deoxyribonucleic acid