Structural insights into human CCAN complex assembled onto DNA

Tian Tian; Lili Chen; Zhen Dou; Zhisen Yang; Xinjiao Gao; Xiao Yuan; Chengliang Wang; Ran Liu; Zuojun Shen; Ping Gui; Maikun Teng; Xianlei Meng; Donald L. Hill; Lin Li; Xuan Zhang; Xing Liu; Linfeng Sun; Jianye Zang; Xuebiao Yao

doi:10.1038/s41421-022-00439-6

Cell Discovery (Sep 2022)

Structural insights into human CCAN complex assembled onto DNA

Tian Tian,
Lili Chen,
Zhen Dou,
Zhisen Yang,
Xinjiao Gao,
Xiao Yuan,
Chengliang Wang,
Ran Liu,
Zuojun Shen,
Ping Gui,
Maikun Teng,
Xianlei Meng,
Donald L. Hill,
Lin Li,
Xuan Zhang,
Xing Liu,
Linfeng Sun,
Jianye Zang,
Xuebiao Yao

Affiliations

Tian Tian: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Lili Chen: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Zhen Dou: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Zhisen Yang: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Xinjiao Gao: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Xiao Yuan: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Chengliang Wang: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Ran Liu: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Zuojun Shen: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Ping Gui: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Maikun Teng: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Xianlei Meng: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Donald L. Hill: Comprehensive Cancer Center, University of Alabama
Lin Li: CAS Center for Excellence in Molecular and Cell Sciences
Xuan Zhang: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Xing Liu: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Linfeng Sun: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Jianye Zang: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China
Xuebiao Yao: MOE Key Laboratory for Cellular Dynamics, the First Affiliated Hospital, CAS Center for Excellence in Biomacromolecules, and School of Life Sciences, University of Science and Technology of China

DOI: https://doi.org/10.1038/s41421-022-00439-6
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 15

Abstract

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Abstract In mitosis, accurate chromosome segregation depends on kinetochores that connect centromeric chromatin to spindle microtubules. The centromeres of budding yeast, which are relatively simple, are connected to individual microtubules via a kinetochore constitutive centromere associated network (CCAN). However, the complex centromeres of human chromosomes comprise millions of DNA base pairs and attach to multiple microtubules. Here, by use of cryo-electron microscopy and functional analyses, we reveal the molecular basis of how human CCAN interacts with duplex DNA and facilitates accurate chromosome segregation. The overall structure relates to the cooperative interactions and interdependency of the constituent sub-complexes of the CCAN. The duplex DNA is topologically entrapped by human CCAN. Further, CENP-N does not bind to the RG-loop of CENP-A but to DNA in the CCAN complex. The DNA binding activity is essential for CENP-LN localization to centromere and chromosome segregation during mitosis. Thus, these analyses provide new insights into mechanisms of action underlying kinetochore assembly and function in mitosis.

Published in Cell Discovery

ISSN: 2056-5968 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/celldisc/

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