The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition
The Aurora B specificity switch is required to protect from non-disjunction at the metaphase/anaphase transition
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DOI：
10.1038/s41467-020-15163-6
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发表时间：
2020-03-13
影响因子：
16.6
通讯作者：
Soliman, Tanya N.
中科院分区：
文献类型：
--
作者：
Kelly, Joanna R.;Martini, Silvia;Soliman, Tanya N.
Aurora B解离检查点延迟胞质分裂，直到裂解沟中捕获的DNA分解。该过程涉及Aurora B S227的PKC β磷酸化。评估是否这种PKC ε-极光B模块提供了一个更广泛利用的细胞周期的基因组保护控制，我们显示极光B磷酸化在S227由PKC β也发生在有丝分裂。Aurora B S227 A的表达表型模仿PKC抑制，绕过了与姐妹染色单体的不分离和连锁相关的进入后期的延迟和消退。这种后期延迟的实现反映在细胞周期依赖性的caspase 7切割后的PKC β激活中; caspase 7的敲低以通过异位表达/产生游离PKC β催化结构域来拯救的方式表型PKC β损失。分子动力学表明，极光B S227磷酸化诱导构象变化，这表明在一个深刻的开关特异性S29拓扑II α磷酸化，一个必要的有丝分裂过程中的连锁决议。
The Aurora B abscission checkpoint delays cytokinesis until resolution of DNA trapped in the cleavage furrow. This process involves PKC epsilon phosphorylation of Aurora B S227. Assessing if this PKC epsilon-Aurora B module provides a more widely exploited genome-protective control for the cell cycle, we show Aurora B phosphorylation at S227 by PKC epsilon also occurs during mitosis. Expression of Aurora B S227A phenocopies inhibition of PKC epsilon in by-passing the delay and resolution at anaphase entry that is associated with non-disjunction and catenation of sister chromatids. Implementation of this anaphase delay is reflected in PKC epsilon activation following cell cycle dependent cleavage by caspase 7; knock-down of caspase 7 phenocopies PKC epsilon loss, in a manner rescued by ectopically expressing/generating a free PKC epsilon catalytic domain. Molecular dynamics indicates that Aurora B S227 phosphorylation induces conformational changes and this manifests in a profound switch in specificity towards S29 TopoII alpha phosphorylation, a response necessary for catenation resolution during mitosis.