在细胞分裂过程中，由相对纺锤体两极发出的微管精确捕获在染色体着丝粒上构建的姐妹动粒，控制着染色体的忠实分离。为了确保姐妹染色单体正确分离，姐妹着丝粒在微管附着之前经过解析以实现双极取向。着丝粒解析失败会增加分粒附着的频率，来自相反两极的微管附着在同一个姐妹着丝粒上，导致染色体滞后、非整倍体，甚至癌症进展。 Aurora B 介导的张力感应机制可纠正错误的着丝粒-微管附着，这一机制已得到充分研究。然而，人们对避免有丝分裂早期发生的粒细胞附着的预防机制知之甚少。在这项研究中，我们发现有丝分裂激酶 Aurora B/AIR-2 的失活会增加秀丽隐杆线虫的细胞附着。一方面，Aurora B/AIR-2 缺陷细胞表现出着丝粒分辨率发生延迟以及凝缩蛋白 II 成分靶向染色质的破坏。另一方面，Aurora B/AIR-2 的缺失导致着丝粒蛋白 CENP-A/HCP-3 和 M18BP1/KNL-2 以及着丝粒蛋白 MIS-12 在染色质上的定位增加，这可能会产生异位动粒导致错误的附着。总之，本研究阐明 Aurora B/AIR-2 调节姐妹着丝粒分辨率和 CENP-A/HCP-3 沉积，以积极预防细胞中的染色体不稳定。© 作者 2024。由牛津大学出版社出版代表中国科学院上海生命科学研究院生物化学与细胞生物学研究所。

During cell division, the accurate capture of sister kinetochores that are built on the centromeres of chromosomes by microtubules emanating from opposite spindle poles governs faithful chromosome segregation. To ensure sister chromatids separate correctly, sister centromeres undergo resolution to achieve bi-polar orientation prior to microtubule attachments. Failure of centromere resolution increases the frequency of merotelic attachments, with microtubules from opposite poles attaching to the same sister kinetochore, causing lagging chromosome, aneuploidy, and even cancer progression. The Aurora B-mediated tension-sensing machinery to correct erroneous kinetochore-microtubule attachments has been well studied. However, preventative mechanisms to avoid merotelic attachments that occur in the earlier mitotic stage are poorly understood. In this study, we found that inactivation of mitotic kinase Aurora B/AIR-2 increases merotelic attachments in Caenorhabditis elegans. On one hand, Aurora B/AIR-2-deficient cells exhibited a delay in the occurrence of centromere resolution and a disruption in targeting condensin II components to chromatin. On the other hand, loss of Aurora B/AIR-2 results in an increased localization of centromeric proteins CENP-A/HCP-3 and M18BP1/KNL-2 as well as the kinetochore protein MIS-12 on chromatin, which may generate ectopic kinetochores causing erroneous attachments. To conclude, this study elucidated that Aurora B/AIR-2 regulates sister centromere resolution and CENP-A/HCP-3 deposition to actively prevent merotely and chromosome instability in cells.© The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.