Fig. 5.

Direct cytotoxic effect of PARP1 inhibitors. A – inhibition of PARP1 leads to inactivation of a repair system and preservation of spontaneously occurring single-strand breaks (SSBs), which causes formation of double-strand breaks. B – because of the action of PARP1 inhibitors, PARP1 remains bound to damaged DNA and, thus, cannot dissociate from it and clear the area for PARP1-dependent repair enzymes. C – in the presence of PARP inhibitors, mutant BRCA1 is less accumulated at the DNA damage site, D – when double-strand breaks occur in HR-deficient cells, another NHEJ system is activated. As a result, repair errors occur that can lead to genomic instability and cell death