A01
Project Area A - Biology and Molecular Oncology
Prof. Dr. Stefan Westermann
Molecular Genetics I
University of Duisburg-Essen
Phone: +49 201 183 2733
Email
Molecular control of kinetochore-microtubule interactions at the metaphase-anaphase transition
During the division of eukaryotic cells, chromosomes have to be distributed precisely in order to ensure that each daughter cell contains the complete genetic blueprint of an entire organism. Errors in this segregation process can lead to unbalanced chromosome numbers, a situation frequently observed in cancer cells.
The kinetochore is one of the most fascinating multi-protein complexes of eukaryotic cells and plays a central role in the chromosome segregation process. A kinetochore consists of hundreds of polypeptides assembled into sophisticated molecular structure that forms a dynamic connection between a chromosome and microtubule filaments. Kinetochores ensure that sister chromatids are captured by the spindle, that attachment errors are corrected and that microtubule-based forces can pull sister chromatids apart.
In the context of this CRC, we will undertake a multidisciplinary, collaborative approach to define the molecular mechanisms that establish kinetochore bi-orientation on the mitotic spindle and thereby trigger the metaphase-anaphase cell state transition in the budding yeast S. cerevisiae. We will use a combination of biochemical reconstitution approaches and high-end imaging to define the molecular requirements for the assembly of a plus-end associated outer kinetochore and to reveal new regulatory mechanisms in the segregation process.
Project Members
Christian Cozma
Richard Pleuger
Publications
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Microtubule end-on attachment maturation regulates Mps1 association with its kinetochore receptorIn: Current Biology Vol. 34 (2024) Nr. 11, pp. 2279 - 2293.e6Online Full Text: dx.doi.org/ (Open Access)
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Systematic analysis of microtubule plus-end networks defines EB-cargo complexes critical for mitosis in budding yeastIn: Molecular Biology of the Cell Vol. 34 (2023) Nr. 5, ar37Online Full Text: dx.doi.org/ Online Full Text (Open Access)
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Cdc4 phospho-degrons allow differential regulation of ame1ceⁿp⁻u protein stability across the cell cycleIn: eLife Vol. 10 (2021) e67390Online Full Text: dx.doi.org/ (Open Access)
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Phospho-regulated Bim1/EB1 interactions trigger Dam1c ring assembly at the budding yeast outer kinetochoreIn: The EMBO Journal Vol. 40 (2021) Nr. 18, e108004Online Full Text: dx.doi.org/ (Open Access)
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Ipl1-controlled attachment maturation regulates Mps1 association with its kinetochore receptor(2023) 43 SeitenOnline Full Text: dx.doi.org/ (Open Access)