Aurora B promotes the CENP-T–CENP-W interaction to guide accurate chromosome segregation in mitosis

Author:

Liu Wei12ORCID,Dou Zhen13ORCID,Wang Chunyue1,Zhao Gangyin1,Wu Fengge1,Wang Chunli4,Aikhionbare Felix2,Ye Mingliang4ORCID,Sedzro Divine Mensah1,Yang Zhenye1,Fu Chuanhai1,Wang Zhikai123,Gao Xinjiao1,Yao Xuebiao13,Song Xiaoyu13,Liu Xing13ORCID

Affiliation:

1. MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China School of Life Sciences , Hefei 230027 , China

2. Keck Center for Cellular Dynamics and Organoids Plasticity , Atlanta, GA 30310 , USA

3. Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, Hefei National Research Center for Interdisciplinary Sciences at the Microscale , Hefei 230026 , China

4. National Chromatographic Research and Analysis Center, Chinese Academy of Sciences , Dalian 116023 , China

Abstract

Abstract Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.

Funder

National Key Research and Development Program of China

Publisher

Oxford University Press (OUP)

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