Cyclin B:CDK 1 is the master kinase regulator of mitosis. We show here that, in addition to its kinase functions, mammalian Cyclin B also scaffolds a localised signalling pathway to help preserve genome stability. Cyclin B1 localises to an expanded region of the outer kinetochore, known as the corona, where it scaffolds the spindle assembly checkpoint (SAC ) machinery by binding directly to MAD 1. In vitro reconstitutions map the key binding interface to a few acidic residues in the N‐terminal region of MAD 1, and point mutations in this sequence abolish MAD 1 corona localisation and weaken the SAC . Therefore, Cyclin B1 is the long‐sought‐after scaffold that links MAD 1 to the corona, and this specific pool of MAD 1 is needed to generate a robust SAC response. Robustness arises because Cyclin B1:MAD 1 localisation loses dependence on MPS 1 kinase after the corona has been established, ensuring that corona‐localised MAD 1 can still be phosphorylated when MPS 1 activity is low. Therefore, this study explains how corona‐MAD 1 generates a robust SAC signal, and it reveals a scaffolding role for the key mitotic kinase, Cyclin B1:CDK 1, which ultimately helps to inhibit its own degradation.

中文翻译：

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细胞周期蛋白 B1 在着丝粒冠处支撑 MAD1 以激活有丝分裂检查点。


细胞周期蛋白 B:CDK 1 是有丝分裂的主要激酶调节因子。我们在此表明​​，除了其激酶功能外，哺乳动物细胞周期蛋白 B 还构建了一个局部信号通路，以帮助保持基因组稳定性。细胞周期蛋白 B1 定位于外着丝粒的扩展区域（称为冠），在该区域中，它通过直接与 MAD 1 结合来支撑纺锤体组装检查点 (SAC) 机制。体外重构将关键结合界面映射到细胞中的一些酸性残基。 MAD 1 的 N 末端区域和该序列中的点突变废除了 MAD 1 的冠状定位并削弱了 SAC 。因此，Cyclin B1 是长期寻求的将 MAD 1 连接到日冕的支架，并且需要这种特定的 MAD 1 库来产生强大的 SAC 响应。稳健性的产生是因为在电晕建立后，Cyclin B1:MAD 1 定位失去了对 MPS 1 激酶的依赖，确保当 MPS 1 活性较低时，电晕定位的 MAD 1 仍然可以被磷酸化。因此，这项研究解释了 corona-MAD 1 如何产生强大的 SAC 信号，并揭示了关键有丝分裂激酶 Cyclin B1:CDK 1 的支架作用，最终有助于抑制其自身降解。