PARP1 and cancer: Since SSBs are among the most frequent endogenous DNA lesions repaired by PARP1 and PARP2, and the discovery of the synthetic lethality of PARP inhibitors in BRCA-deficient cells, the mechanism by which PARPIs exert their cytotoxicity has been dominantly interpreted as an accumulation of SSBs resulting in lethal DNA double-strand breaks upon replication stalling in cancer cells defective in homologous recombination (HR) [5, 6].