Proposed model of DFF40/CAD involvement in both apoptotic hallmarks during caspase-dependent cell death in tumor-derived cells. After apoptotic insult, DFF40/CAD is released from its inhibitor ICAD and, therefore, activated. On one hand, the endonuclease will induce SSBs, promoting nuclear collapse/disassembly (stage II). On the other hand, possibly in a second step, DFF40/CAD will degrade the chromatin into oligonucleosomal-size DSBs, generating the DNA ladder. The stage I apoptotic nuclear morphology and HMW DNA fragmentation are DFF40/CAD-independent processes.