A. Schematic diagram of the I-PpoI system for inducing DNA breaks in the nuclear human genome. Addition of 4-OHT to U-2-OS-pEP15 cells stably expressing the I-PpoI endonuclease fused to the estrogen receptor (ER) induces nuclear translocation of the fusion protein and cleavage cleavage of FokI recognition sites in nuclear DNA resulting, leading to DSB induction. 