Journal
EXPERIMENTAL CELL RESEARCH
Volume 269, Issue 2, Pages 193-201Publisher
ELSEVIER INC
DOI: 10.1006/excr.2001.5293
Keywords
actinomycin D; apoptosis; caspases; PARP-1; poly(ADP-ribose)
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Poly(ADP-ribose) polymerase-1 (PARP-1) plays the active role of nick sensor during DNA repair and apoptosis, when it synthesizes ADP-ribose from NAD(+) in the presence of DNA strand breaks. Moreover, PARP-1 becomes a target of apoptotic caspases, which originate two proteolytic fragments of 89 and 24 kDa. The precise relationship between PARP-1 activation and degradation during apoptosis is still a matter of debate. In human Hep-2 cells driven to apoptosis by actinomycin D, we have monitored PARP-1 activity by the mAb 10H, which is specific for the ADP-ribose polymers, and we have observed that poly(ADP-ribose) synthesis is a very early response to the apoptotic stimulus. The analysis of the presence and fate of the p89 proteolytic fragment revealed that PARP-1 proteolysis by caspases is concomitant with poly(ADP-ribose) synthesis and that p89 migrates from the nucleus into the cytoplasm in late apoptotic cells with advanced nuclear fragmentation. (C) 2001 Academic Press.
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