*Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
Biochem Soc Trans. 2013 Dec;41(6):1761-5. doi: 10.1042/BST20130191.
Correct transmission of genetic information from mother to daughter cells is necessary for development and survival. Accurate segregation is achieved by bipolar attachment of sister kinetochores in each chromatid pair to spindle microtubules emanating from opposite spindle poles, a process known as chromosome bi-orientation. Achieving this requires dynamic interplay between kinetochore proteins, kinesin motor proteins and cell cycle regulators. Chromosome bi-orientation is monitored by a surveillance mechanism known as the SAC (spindle assembly checkpoint). The Aurora B kinase, which is bound to the inner centromere during early mitosis, plays a central role in both chromosome bi-orientation and the spindle checkpoint. The application of tension across centromeres establishes a spatial gradient of high phosphorylation activity at the inner centromere and low phosphorylation activity at the outer kinetochore. This gradient is further refined by the association of PP1 (protein phosphatase 1) to the outer kinetochore, which stabilizes kinetochore-microtubule interactions and silences the spindle checkpoint by dephosphorylating Aurora B kinase targets when chromosome bi-orientation is achieved. In the present review, I discuss emerging evidence that bidirectional cross-talk between mitotic kinesins and the Aurora kinase-PP1 axis is crucial for co-ordinating chromosome bi-orientation and spindle checkpoint signalling in eukaryotes.
从母亲到子细胞的遗传信息的正确传递对于发育和生存是必要的。姐妹动粒在每条染色单体对中的双极附着到来自纺锤体相对两极的纺锤体微管，这一过程被称为染色体双定向，从而实现精确的分离。实现这一点需要动粒蛋白、驱动蛋白马达蛋白和细胞周期调节剂之间的动态相互作用。染色体双定向由称为纺锤体组装检查点（SAC）的监测机制监测。在早期有丝分裂过程中与着丝粒内圈结合的 Aurora B 激酶在染色体双定向和纺锤体检查点中都起着核心作用。在着丝粒上施加张力会在着丝粒内圈建立高磷酸化活性的空间梯度，而在外动粒上则磷酸化活性较低。通过将 PP1（蛋白磷酸酶 1）与外动粒结合，进一步细化了这种梯度，这通过去磷酸化 Aurora B 激酶靶标来稳定动粒-微管相互作用并沉默纺锤体检查点，从而实现染色体双定向。在本综述中，我讨论了新出现的证据，即有丝分裂驱动蛋白和 Aurora 激酶-PP1 轴之间的双向交流对于协调真核生物中的染色体双定向和纺锤体检查点信号至关重要。
