Figure 7.

Model for control of premature mitosis during DNA replication stress. Mitosis is triggered when activated CDK1 binds to its regulatory partner cyclinB. During DNA replication stress, activation of ATR elicits phosphorylation of CHK1 that, in turn, phosphorylates CDC25A, targeting it for ubiquitin-mediated degradation. In the absence of CDC25A, pTyr15 CDK1 is not dephosphorylated to active CDK1 thus preventing the onset of mitosis. In CHK1-depleted HCT116 cells, CDK1 phosphorylation at Tyr15 is unexpectedly sustained, which should suppress the initiation of mitosis. However, our work indicates that activated CHK1 also suppresses phosphorylation of Aurora B to prevent premature entry into mitosis in cells arrested in S-phase (left). When CHK1 is depleted, Aurora B autophosphorylation is no longer suppressed leading to its activation, histone H3 phosphorylation and premature chromosome condensation (right)