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Reconstitution of a 26-Subunit human kinetochore reveals cooperative microtubule binding by CENP-OPQUR and NDC80
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Pesenti, Marion E., Prumbaum, Daniel, Auckland, Philip, Smith, Charlotte M., Faesen, Alex C., Petrovic, Arsen, Erent, Muriel, Maffini, Stefano, Pentakota, Satyakrishna, Weir, John R., Lin, Yu-Chih, Raunser, Stefan, McAinsh, Andrew D. and Musacchio, Andrea (2018) Reconstitution of a 26-Subunit human kinetochore reveals cooperative microtubule binding by CENP-OPQUR and NDC80. Molecular Cell, 71 (6). pp. 923-939. doi:10.1016/j.molcel.2018.07.038 ISSN 1097-2765.
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Official URL: https://doi.org/10.1016/j.molcel.2018.07.038
Abstract
The approximately thirty core subunits of kinetochores assemble on centromeric chromatin containing the histone H3 variant CENP-A and connect chromosomes with spindle microtubules. The chromatin proximal 16-subunit CCAN (constitutive centromere associated network) creates a mechanically stable bridge between CENP-A and the kinetochore's microtubule-binding machinery, the 10-subunit KMN assembly. Here, we reconstituted a stoichiometric 11-subunit human CCAN core that forms when the CENP-OPQUR complex binds to a joint interface on the CENP-HIKM and CENP-LN complexes. The resulting CCAN particle is globular and connects KMN and CENP-A in a 26-subunit recombinant particle. The disordered, basic N-terminal tail of CENP-Q binds microtubules and promotes accurate chromosome alignment, cooperating with KMN in microtubule binding. The N-terminal basic tail of the NDC80 complex, the microtubule-binding subunit of KMN, can functionally replace the CENP-Q tail. Our work dissects the connectivity and architecture of CCAN and reveals unexpected functional similarities between CENP-OPQUR and the NDC80 complex. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.]
Item Type: | Journal Article | |||||||||||||||||||||
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Subjects: | Q Science > QH Natural history | |||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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SWORD Depositor: | Library Publications Router | |||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Microtubules, Centromere | |||||||||||||||||||||
Journal or Publication Title: | Molecular Cell | |||||||||||||||||||||
Publisher: | Cell Press | |||||||||||||||||||||
ISSN: | 1097-2765 | |||||||||||||||||||||
Official Date: | 20 September 2018 | |||||||||||||||||||||
Dates: |
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Volume: | 71 | |||||||||||||||||||||
Number: | 6 | |||||||||||||||||||||
Page Range: | pp. 923-939 | |||||||||||||||||||||
DOI: | 10.1016/j.molcel.2018.07.038 | |||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||
Date of first compliant deposit: | 19 September 2018 | |||||||||||||||||||||
Date of first compliant Open Access: | 19 September 2018 | |||||||||||||||||||||
RIOXX Funder/Project Grant: |
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