Figure 1. Mechanism of sensitivity to PARP inhibition in BRCA-deficient cells.
Cells acquire DNA damage through environmental exposures or chemotherapy agents. Repair of single-strand breaks relies on PARP; repair of double-strand breaks depends on BRCA. With PARP inhibition, single-strand breaks progress to double-strand breaks. In the absence of functional BRCA, the accumulation of double-strand breaks overwhelms DNA repair mechanisms. Irreparable DNA damage triggers cell death. DSB, double-strand break; NHEJ, non-homologous end joining; PARP, poly-ADP ribose polymerase; SSA, single-strand annealing; SSB, single-strand break.