The cell cycle is a complex process whose integrity is tightly regulated by a number of checkpoints. When these controls fail, the cell can enter mitosis before DNA repair is completed. In such an event, the dysregulation of mitosis can result in mitotic catastrophe, followed by apoptotic or necrotic cell death. Until now, the signals that determine and trigger these different modes of cell death remained unclear. Here, Boris Zhivotovsky and co-workers (p. 2951) describe a new mechanism that leads to p53-dependent apoptosis following DNA damage induced through mitotic catastrophe. They show that, in an attempt to exit from defective mitosis as a result of unrepaired DNA damage, cells create anaphase bridges, which leads to the formation of additional DNA breaks during the progression from anaphase to telophase. Subsequently, these breakage–fusion–bridge cycles result in increased γH2AX phosphorylation, which then triggers an apoptotic death signal that involves ATM (ataxia telangiectasia...

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