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SKAP interacts with Aurora B to guide end-on capture of spindle microtubules via phase separation 
Manjuan Zhang1,2,† , Fengrui Yang1,2,3,† , Wenwen Wang1,2 , Najdat Zohbi3 , Xiwei Wang1,2,3 , Dongmei Wang1,2,3 , Xiaoxuan Zhuang1 , Zhen Dou1,2 , Dan Liu1 , Xiaoyu Song1,2,3 , Hadiyah-Nicole Green3 , Xing Liu1,* , Xuebiao Yao1,*
1MOE Key Laboratory for Cellular Dynamics and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China
2Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and CAS Center for Excellence in Molecular Cell Science, Hefei 230027, China
3Keck Center for Organoids Plasticity Control, Morehouse School of Medicine, Atlanta, GA 30310, USA
These authors contributed equally to this work.
*Correspondence to:Xing Liu , Email:xing1017@ustc.edu.cn Xuebiao Yao , Email:yaoxb@ustc.edu.cn
J Mol Cell Biol, Volume 13, Issue 12, December 2021, 841-852,  https://doi.org/10.1093/jmcb/mjab058
Keyword: Aurora B, SKAP, kinase activity, mitosis, phase separation

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent studies show that mitotic motor CENP-E cooperates with SKAP and forms a link between kinetochore core MIS13 complex and spindle microtubule plus-ends to achieve accurate chromosome alignment in mitosis. However, it remains elusive how SKAP regulates kinetochore attachment from lateral association to end-on attachment during metaphase alignment. Here, we identify a novel interaction between Aurora B and SKAP that orchestrates accurate interaction between the kinetochore and dynamic spindle microtubules. Interestingly, SKAP spontaneously phase-separates in vitro via weak, multivalent interactions into droplets with fast internal dynamics. SKAP and Aurora B form heterogeneous coacervates in vitro, which recapitulate the dynamics and behavior of SKAP comets in vivo. Importantly, SKAP interaction with Aurora B via phase separation is essential for accurate chromosome segregation and alignment. Based on those findings, we reason that SKAP–Aurora B interaction via phase separation constitutes a dynamic pool of Aurora B activity during the lateral to end-on conversion of kinetochore–microtubule attachments to achieve faithful cell division.