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. 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-binding 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.
Kim
J W
JW
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
Won
J
J
Sohn
S
S
Joe
C O
CO
D017209:Apoptosis / Q000528:radiation effects; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D017354:Point Mutation; D011064:Poly Adenosine Diphosphate Ribose / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D014466:Ultraviolet Rays
D011064:Poly Adenosine Diphosphate Ribose; D004247:DNA