PARP-1 and cellular responses to DNA damage. The intensity of DNA damage determines cellular pathways: survival, apoptosis, or necrosis. In the case of mild DNA damage, poly(ADP-ribosylation) enhances DNA repair and thus cell survival. When the damage is beyond repair, PARP-1 facilitates apoptosis, preventing ATP depletion and DNA repair through PARP-1 caspase-mediated cleavage. Severe DNA damage leads to PARP-1 overactivation, cellular energy depletion, and necrotic cell death. Figure is adapted from Virág and Szabó, in 2002 [70].