Defying death after DNA damage

Abstract

DNA damage frequently triggers death by apoptosis. The irreversible decision to die can be facilitated or forestalled through integration of a wide variety of stimuli from within and around the cell. Here we address some fundamental questions that arise from this model. Why should DNA damage initiate apoptosis in the first place? In damaged cells, what are the alternatives to death and why should they be selected in some circumstances but not others? What signals register DNA damage and how do they impinge on the effector pathways of apoptosis? Is there a suborganellar apoptosome complex effecting the integration of death signals within the nucleus, just as there is in the cytoplasm? And what are the consequences of failure to initiate apoptosis in response to DNA damage?