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Microtubule end-on attachment maturation regulates Mps1 association with its kinetochore receptor
Open accessPublished version of a preprint
Abstract
Faithful chromosome segregation requires that sister chromatids establish bi-oriented kinetochore-microtubule attachments. The spindle assembly checkpoint (SAC) prevents premature anaphase onset with incomplete attachments. However, how microtubule attachment and checkpoint signaling are coordinated remains unclear. The conserved kinase Mps1 initiates SAC signaling by localizing transiently to kinetochores in prometaphase and is released upon bi-orientation. Using biochemistry, structure predictions, and cellular assays, we shed light on this dynamic behavior in Saccharomyces cerevisiae. A conserved N-terminal segment of Mps1 binds the neck region of Ndc80:Nuf2, the main microtubule receptor of kinetochores. Mutational disruption of this interface, located at the backside of the paired CH domains and opposite the microtubule-binding site, prevents Mps1 localization, eliminates SAC signaling, and impairs growth. The same interface of Ndc80:Nuf2 binds the microtubule-associated Dam1 complex. We demonstrate that the error correction kinase Ipl1/Aurora B controls the competition between Dam1 and Mps1 for the same binding site. Thus, binding of the Dam1 complex to Ndc80:Nuf2 may release Mps1 from the kinetochore to promote anaphase onset.
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Metadata
- Authors
- Pleuger, R., Cozma, C., Hohoff, S., Denkhaus, C., Dudziak, A., Kaschani, F., Kaiser, M., Musacchio, A., Vetter, I. R., & Westermann, S.
- Affiliations
- University of Duisburg-Essen (DE)
- Max Planck Institute of Molecular Physiology (DE)
- Corresponding author
- Westermann, Stefan
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 34
- Issue
- 11
- Pages
- 2279-2293.e6
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W4398167221
- Cited by
- 22
- References
- 2
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 6
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (424228829, SFB1430)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Mps1 kinase, spindle assembly checkpoint, kinetochore-microtubule attachment, Dam1 complex, kinetochore, chromosome segregation, Saccharomyces cerevisiae, checkpoint signaling
- MeSH terms
- Microtubule-Associated Proteins, Microtubules, Nuclear Proteins, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Kinetochores, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins
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