DNA-binding activity of the N-terminal cleavage product of poly(ADP-ribose) polymerase is required for UV mediated apoptosis

The role of the N-terminal cleavage product of poly(ADP-ribose) polymerase (PARP) on UV mediated apoptosis was investigated in cultured HeLa cells. Ul trastructural analysis of cells expressing caspase-resistant PARP (PARP(D21 4A)) revealed the typical features of necrosis following UV treatment. Howe ver, cells co-expressing PARP(D214A) With the N-terminal fragment of PARP c ontaining the DNA-binding domain underwent apoptosis instead of necrosis. I n this study, we have demonstrated that the DNA-binding activity of the N-t erminal fragment of PARP is important for the execution of apoptosis. Point mutations were introduced in the DNA-hinding sites of the N-terminal fragm ent. Cells co-expressing PARP(D214A) With the mutated N-terminal fragments neither stimulated apoptosis nor prevented necrosis in response to UV irrad iation. The present study proposes that the DNA-binding activity of the N-t erminal fragment of PARP in UV treated cells prevents cellular ATP depletio n, a mechanism by which necrotic cell death is triggered.