Early stages of p53-induced apoptosis are reversible

Apoptosis is a type of physiological cell death that occurs during developm ent, normal tissue homeostasis, or as a result of different cellular insult s. The phenotype of an apoptotic cell is relatively consistent in most case s of apoptosis and involves at least changes in the cell membrane, proteoly sis of cytoplasmic and nuclear proteins, and eventual destruction of nuclea r DNA, Our laboratory is interested in the reversibility of apoptosis. We h ave initial evidence that DNA repair is activated early in p53-induced apop tosis and may be involved in its reversibility. The present work further st rengthens our proposition that p53-induced apoptosis is reversible. Weshow that p53 activation induces phosphatidylserine (PS) externalization early i n apoptosis, and that these early apoptotic cells with externalized PS can be rescued and proliferate if the apoptotic stimulus is removed. In additio n, we show that unscheduled DNA synthesis occurs in early apoptotic cells, and that if DNA repair is inhibited by aphidicolin, apoptosis is accelerate d. These results confirm that early p53-induced apoptotic cells can be resc ued from the apoptotic program, and that DNA repair can modulate that cell death process.