Bekier Michael E, Mazur Travis, Rashid Maisha S, Taylor William R
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, MS 601, Toledo, Ohio 43606, USA.
Nat Commun. 2015 Apr 9;6:6775. doi: 10.1038/ncomms7775.
The chromosomal passenger complex (CPC) localizes to centromeres where it activates the mitotic checkpoint in response to inappropriate inter-kinetochore tension. This error correction function is essential for proper chromosome segregation. Here we define several critical features of CPC localization and function. First, the Borealin dimerization domain suppresses dynamic exchange at the centromere to allow optimal CPC function. Second, Borealin dimerization is essential to target a subpopulation of CPC proximal to the kinetochore when the mitotic spindle is disrupted. This subpopulation is also needed for full CPC checkpoint function. The existence of a pool of CPC at the kinetochore suggests that error correction is more complicated than predicted from the Aurora B phosphorylation gradient model. Finally, Haspin kinase plays a key role in maintaining the slowly exchanging centromere Borealin pool, while Aurora B and Mps1 play minimal roles in maintaining CPC localization once cells are in mitosis.
染色体乘客复合体（CPC）定位于着丝粒，在那里它会响应不适当的动粒间张力激活有丝分裂检查点。这种纠错功能对于正确的染色体分离至关重要。在这里，我们定义了CPC定位和功能的几个关键特征。首先，Borealin二聚化结构域抑制着丝粒处的动态交换，以实现最佳的CPC功能。其次，当有丝分裂纺锤体被破坏时，Borealin二聚化对于将CPC的一个亚群靶向到靠近动粒的位置至关重要。这个亚群对于完整的CPC检查点功能也是必需的。动粒处存在CPC池表明，纠错比极光B磷酸化梯度模型预测的更为复杂。最后，Haspin激酶在维持缓慢交换的着丝粒Borealin池中起关键作用，而一旦细胞进入有丝分裂，极光B和Mps1在维持CPC定位方面起的作用最小。
