Accurate chromosome segregation in mitosis requires sister kinetochores to bind to microtubules from opposite spindle poles. The stability of kinetochore-microtubule attachments is fine-tuned to prevent or correct erroneous attachments while preserving amphitelic interactions. Polo kinase has been implicated in both stabilizing and destabilizing kinetochore-microtubule attachments. However, the mechanism underlying Polo-destabilizing activity remains elusive. Here, resorting to an RNAi screen in Drosophila for suppressors of a constitutively active Polo mutant, we identified a strong genetic interaction between Polo and the Rod-ZW10-Zwilch (RZZ) complex, whose kinetochore accumulation has been shown to antagonize microtubule stability. We find that Polo phosphorylates Spindly and impairs its ability to bind to Zwilch. This precludes dynein-mediated removal of the RZZ from kinetochores and consequently delays the formation of stable end-on attachments. We propose that high Polo-kinase activity following mitotic entry directs the RZZ complex to minimize premature stabilization of erroneous attachments, whereas a decrease in active Polo in later mitotic stages allows the formation of stable amphitelic spindle attachments. Our findings demonstrate that Polo tightly regulates the RZZ-Spindly-dynein module during mitosis to ensure the fidelity of chromosome segregation.

中文翻译：

---

Polo 调节 Spindly 以防止动粒-微管附着物过早稳定。


有丝分裂中准确的染色体分离需要姐妹动粒与相反纺锤体极的微管结合。着丝粒-微管附着的稳定性经过微调，以防止或纠正错误的附着，同时保留两性相互作用。 Polo 激酶与着丝粒-微管附着的稳定和不稳定有关。然而，马球破坏稳定活动的潜在机制仍然难以捉摸。在这里，通过在果蝇中对 Polo 突变体的抑制子进行 RNAi 筛选，我们发现了 Polo 和 Rod-ZW10-Zwilch (RZZ) 复合体之间存在很强的遗传相互作用，该复合体的动粒积累已被证明会拮抗微管的稳定性。我们发现 Polo 磷酸化 Spindly 并削弱其与 Zwilch 结合的能力。这阻止了动力蛋白介导的 RZZ 从动粒的去除，从而延迟了稳定的末端附着的形成。我们提出，有丝分裂进入后的高 Polo 激酶活性指导 RZZ 复合体最大限度地减少错误附着的过早稳定，而有丝分裂后期活性 Polo 的减少允许形成稳定的两性纺锤体附着。我们的研究结果表明，Polo 在有丝分裂过程中严格调节 RZZ-Spindly-dynein 模块，以确保染色体分离的保真度。