Poly (ADP-ribose) polymerase cleavage during apoptosis: when and where?

C Soldani, MC Lazzè, MG Bottone, G Tognon… - Experimental cell …, 2001 - Elsevier
Experimental cell research, 2001Elsevier
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 …
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.
Elsevier
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