Figure 6
Mitotic arrest initiates a caspase-dependent telomere damage response.
Prolonged mitotic arrest promotes the time-dependent destruction of Mcl-1 after its phosphorylation by CDK1-cyclin B. Mcl-1 loss promotes caspase activation and the activation of the endonuclease CAD, resulting in selective DNA double-strand breaks at telomeres, activation of DNA-PK, TRF2 loss from telomeres and formation of γH2AX. If caspase activation exceeds a threshold, it may result in apoptosis direct from mitosis, but if mitotic slippage caused by the slow destruction of cyclin B precedes this threshold, then cells respond in interphase through a full DNA damage response (DDR) and p53 activation. Activation of DNA repair mechanisms can cause telomere fusions leading to chromosome instability.
