Poly(ADP-ribose) Polymerase Cleavage during Apoptosis: When and Where?

• DOI: 10.1006/excr.2001.5293
• Publication Date: 2002-09-16T15:46:35Z
• Authors: Cristiana Soldani; Maria Claudia Lazzè; Maria Grazia Bottone; Gianluca Tognon; Marco Biggiogera; Carlo E. Pellicciari; A.Ivana Scovassi
• Keywords: Proteolysis; Apoptotic DNA fragmentation; Fragmentation

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.