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

Poly(ADP-ribose) polymerase-1 (PARP-1) plays the active role of "nick senso r" 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 t hat poly(ADP-ribose) synthesis is a very early response to the apoptotic st imulus. The analysis of the presence and fate of the p89 proteolytic fragme nt revealed that PARP-1 proteolysis by caspases is concomitant with poly(AD P-ribose) synthesis and that p89 migrates from the nucleus into the cytopla sm in late apoptotic cells with advanced nuclear fragmentation. (C) 2001 Ac ademic Press.