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

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The role of the N-terminal cleavage product of poly(ADP-ribose) polymerase (PARP) on UV mediated apoptosis was investigated in cultured HeLa cells. Ultrastructural analysis of cells expressing caspase-resistant PARP (PARP(D214A)) revealed the typical features of necrosis following UV treatment. However, cells co-expressing PARP(D214A) With the N-terminal fragment of PARP containing the DNA-binding domain underwent apoptosis instead of necrosis. In this study, we have demonstrated that the DNA-binding activity of the N-terminal fragment of PARP is important for the execution of apoptosis. Point mutations were introduced in the DNA-hinding sites of the N-terminal fragment. Cells co-expressing PARP(D214A) With the mutated N-terminal fragments neither stimulated apoptosis nor prevented necrosis in response to UV irradiation. The present study proposes that the DNA-binding activity of the N-terminal fragment of PARP in UV treated cells prevents cellular ATP depletion, a mechanism by which necrotic cell death is triggered.
Publisher
Company Of Biologists Ltd
Issue Date
2000-03
Language
ENG
Article Type
Article
Appears in Collection
BS-Journal Papers(저널논문)
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