PARP1 and cancer: Consistent with the importance of PARP in DNA repair, inhibition of PARP activity in homologous recombination (HR)-deficient cells (such as those with BRCA and PALB2 mutations) induces cell death due to a mechanism known as ‘synthetic lethality’, as it is difficult for cancer cells to tolerate simultaneous loss of both PARP-dependent SSB repair and HR-mediated double-strand break (DSB) repair machinery.