Kinetochores form the interface between chromosomes and spindle microtubules and are thus under tight control by a complex regulatory circuitry. The Aurora B kinase plays a central role within this circuitry by destabilizing improper kinetochore-microtubule attachments and relaying the attachment status to the spindle assembly checkpoint. Intriguingly, Aurora B is conserved even in kinetoplastids, a group of early-branching eukaryotes which possess a unique set of kinetochore proteins. It remains unclear how their kinetochores are regulated to ensure faithful chromosome segregation. Here, we show in Trypanosoma brucei that Aurora B activity controls the metaphase-to-anaphase transition through phosphorylation of the divergent Bub1-like protein KKT14. Depletion of KKT14 overrides the metaphase arrest resulting from Aurora B inhibition, while expression of non-phosphorylatable KKT14 delays anaphase onset. Finally, we demonstrate that re-targeting Aurora B to the outer kinetochore suffices to promote mitotic exit but causes extensive chromosome missegregation in anaphase. Our results indicate that Aurora B and KKT14 are involved in an unconventional circuitry controlling cell cycle progression in trypanosomes.

中文翻译：

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Aurora B 控制锥虫中的后期发作和无错误的染色体分离。


着丝粒形成染色体和纺锤体微管之间的界面，因此受到复杂调节回路的严格控制。Aurora B 激酶通过破坏不正确的着丝粒-微管附着并将附着状态传递给纺锤体组装检查点，在该回路中发挥核心作用。有趣的是，Aurora B 即使在动质体中也是保守的，动质体是一组具有独特动粒蛋白的早期分支真核生物。目前尚不清楚它们的着丝粒是如何被调节以确保忠实的染色体分离的。在这里，我们在布鲁氏锥虫中表明，Aurora B 活性通过磷酸化不同的 Bub1 样蛋白 KKT14 来控制中期到后期的转变。KKT14 的耗竭覆盖了 Aurora B 抑制导致的中期停滞，而不可磷酸化的 KKT14 的表达延迟了后期开始。最后，我们证明将 Aurora B 重新定位到外部着丝粒足以促进有丝分裂退出，但会导致后期广泛的染色体错误分离。我们的结果表明，Aurora B 和 KKT14 参与控制锥虫细胞周期进程的非常规电路。