Fig. 1

DNA single-strand break and double-strand break repair pathways. a PARP catalytic cycle and PARP inhibitor. PARP is a core DNA damage sensor in DDR, which binds to damaged DNA lesions, catalyzes the generation of negatively charged poly (ADP-ribose) chains, remodels the structures of damaged chromatin, and recruits DNA repair-related protein complex. Then, PARP is dissociated from DNA damage site by auto-PARylation. PARPi could interfere with the interaction between PARP and its cofactor (β-NAD), inhibit PARylation activity, and trap PARP on damaged DNA chain. b Double-strand break repair pathways. In normal cells, when both HR and NHEJ pathways are available in G2/M stage, HR pathway is preferentially adopted to repair DSB. HR is an effective repair approach with high fidelity which uses the sister copy of damaged sites as the template. However, for some cancer cells with HR deficiency such as BRCA1/2 mutations, NHEJ pathway is utilized for DSB repair. NHEJ is an error-prone repair pathway with low-fidelity which could induce unsustainable DNA damages (e.g., chromosomal rearrangements and mutations) and eventual cell death. β-NAD, β-nicotinamide adenine dinucleotide; DDR, DNA damage response; NHEJ, nonhomologous end joining; HR, homologous recombination; SSB, single-strand break; DSB, double-strand break