Figure 1.

Synthetic lethality for PARP and BRCA.

Notes: PARP1 is activated by DNA damage (a single-strand break represented by red cross), in the presence of a PARP inhibitor. BER is blocked and, on replication, this single-strand break becomes a double-strand break. In normal healthy cells with functional HRR, this is repaired and the cell survives. In cells with HRR deficiency, ie, through BRCA mutations, the break is not repaired or repaired by error-prone NHEJ or MMEJ resulting in genomic instability and ultimately cell death.

Abbreviations: 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.