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  Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation

Maciejowski, J., Drechsler, H., Grundner-Culemann, K., Ballister, E. R., Rodriguez-Rodriguez, J.-A., Rodriguez-Bravo, V., et al. (2017). Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation. Developmental Cell, 41(2), 143-156.e6. doi:10.1016/j.devcel.2017.03.025.

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 Creators:
Maciejowski, John1, Author
Drechsler, Hauke1, Author
Grundner-Culemann, Kathrin2, Author              
Ballister, Edward R.1, Author
Rodriguez-Rodriguez, Jose-Antonio1, Author
Rodriguez-Bravo, Veronica1, Author
Jones, Mathew J. K.1, Author
Foley, Emily1, Author
Lampson, Michael A.1, Author
Daub, Henrik2, Author              
McAinsh, Andrew D.1, Author
Jallepalli, Prasad V.1, Author
Affiliations:
1external, ou_persistent22              
2Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565172              

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Free keywords: SPINDLE ASSEMBLY CHECKPOINT; AURORA B KINASE; MITOTIC CHECKPOINT; CENP-E; QUANTITATIVE PHOSPHOPROTEOMICS; B56-PP2A PHOSPHATASE; INTERACTION NETWORKS; ANAPHASE ONSET; CELL-CYCLE; PHOSPHORYLATIONCell Biology; Developmental Biology;
 Abstract: The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the efficiency of the Ska complex's conversion from lattice diffusion to end-coupled microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation.

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Language(s): eng - English
 Dates: 2017-04-242017
 Publication Status: Published in print
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Developmental Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 41 (2) Sequence Number: - Start / End Page: 143 - 156.e6 Identifier: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134