Poly(ADP-Ribose) Polymerase 1 (PARP-1), when activated by breaks in DNA, poly ADP-ribosylates nuclear proteins, resulting in NAD+ depletion and cell death by apoptosis. During apoptosis, Caspase 3 cleaves PARP into signature 85 and 24 kDa fragments. The 24 kDa fragment irreversibly binds to the broken ends of DNA, preventing access of repair enzymes to DNA, and ensuring the irreversibility of apoptosis. PARP cleavage is commonly used as a marker to "prove" cell death by apoptosis versus necrosis. Western blot detection of PARP cleavage (appearance of the 85 kDa fragment) is widely used as a readout of apoptosis.