A02

© UDE/Bettina Engel-Albustin

Project Area A - Biology and Molecular Oncology

Prof. Dr. Andrea Musacchio

Mechanistic Cell Biology

Max-Planck Institute of Molecular Physiology, Dortmund

Phone: +49 231 133 2101
Email

Bridging the gap between cell biology and biochemistry with artificial protein prosthetics in cell cycle transitions

Mitosis is the process of somatic cell division. It allows humans to develop from a single cell to the ~15 trillion cells of an adult individual. In most cases, dividing cells complete this process without errors, allowing the two daughters of a mother cell to remain genetically identical. Errors in this process, however rare, derange cell physiology and promote the transformation of healthy cells into malignant counterparts. From a molecular perspective, transmission of the genetic material is no easy task, but specialized machinery evolved to execute this fundamental chore seamlessly and accurately. We aim to dissect the molecular basis of mitosis. Because mitosis is rapid, typically requiring less than 1 hour, we study this process with perturbations that trigger immediately observable effects. Working at the interface between biochemistry in reconstituted systems and classical cell biology, we will shed light on fundamental aspects of the chromosome transmission process.

Project Members

Luis Demuth

luis-frederik.demuth@mpi-dortmund.mpg.de

Jason Mak

jason.mak@mpi-dortmund.mpg.de

Publications

    Journal articles

  • Walstein, Kai; Hill, Louisa; Vogt, Doro; Oberste-Lehn, Lina; Janning, Petra; Vetter, Ingrid R; Pan, Dongqing; Musacchio, Andrea
    M18BP1 valency and a distributed interaction footprint determine epigenetic centromere specification in humans
    In: The EMBO Journal, 2026, in press
    DOI (Open Access)
  • Esposito-Verza, Arianna; Conti, Duccio; Rodrigues Pedroso, Paulo D.; Oberste-Lehn, Lina; Koerner, Carolin; Wohlgemuth, Sabine; Mansurkhodzhaev, Artem; Vetter, Ingrid R.; Pesenti, Marion E.; Musacchio, Andrea
    Molecular requirements for PLK1 activation by T-loop phosphorylation
    In: The EMBO Journal, 2026, in press
    DOI (Open Access)
  • Borsellini, Alessandro; Conti, Duccio; Cutts, Erin E.; Harris, Rebecca J.; Walstein, Kai; Graziadei, Andrea; Cecatiello, Valentina; Aarts, Tom F.; Xie, Ren; Mazouzi, Abdelghani; Sen, Sushweta; Hoencamp, Claire; Pleuger, Richard; Ghetti, Sabrina; Oberste-Lehn, Lina; Pan, Dongqing; Bange, Tanja; Haarhuis, Judith H.I.; Perrakis, Anastassis; Brummelkamp, Thijn R.; Rowland, Benjamin D.; Musacchio, Andrea; Vannini, Alessandro
    Condensin II activation by M18BP1
    In: Molecular Cell, Vol. 85, 2025, Nr. 14, pp. 2688 – 2700.e11
    DOI (Open Access)
  • Esposito-Verza, Arianna; Musacchio, Andrea; Conti, Duccio
    Decoding the language of PLK1 docking motifs and activation mechanisms
    In: Trends in Cell Biology, 2025, in press
    DOI (Open Access)
  • Schweighofer, Julia; Mulay, Bhagyashree; Hoffmann, Ingrid; Vogt, Doro; Pesenti, Marion E.; Musacchio, Andrea
    Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT
    In: The Journal of Cell Biology (JCB), Vol. 224, 2025, Nr. 5, e202412042
    DOI (Open Access)
  • Sethi, Suruchi; Ghetti, Sabrina; Cmentowski, Verena; Guerriere, Teresa Benedetta; Stege, Patricia; Piano, Valentina; Musacchio, Andrea
    Interplay of kinetochores and catalysts drives rapid assembly of the mitotic checkpoint complex
    In: Nature Communications, Vol. 16, 2025, Nr. 1, 4823
    DOI (Open Access)
  • Cmentowski, Verena; Musacchio, Andrea
    The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona
    In: Science Advances, Vol. 11, 2025, Nr. 37, eady6890
    DOI (Open Access)
  • Pleuger, Richard; Cozma, Christian; Hohoff, Simone; Denkhaus, Christian; Dudziak, Alexander; Kaschani, Farnusch; Kaiser, Markus; Musacchio, Andrea; Vetter, Ingrid R.; Westermann, Stefan
    Microtubule end-on attachment maturation regulates Mps1 association with its kinetochore receptor
    In: Current Biology, Vol. 34, 2024, Nr. 11, pp. 2279 – 2293.e6
    DOI (Open Access)
  • Conti, Duccio; Verza, Arianna Esposito; Pesenti, Marion E.; Cmentowski, Verena; Vetter, Ingrid R.; Pan, Dongqing; Musacchio, Andrea
    Role of protein kinase PLK1 in the epigenetic maintenance of centromeres
    In: Science, Vol. 385, 2024, Nr. 6713, pp. 1091 – 1097
    DOI
  • Polley, Soumitra; Raisch, Tobias; Ghetti, Sabrina; Körner, Marie; Terbeck, Melina; Gräter, Frauke; Raunser, Stefan; Aponte-Santamaría, Camilo; Vetter, Ingrid R.; Musacchio, Andrea
    Structure of the human KMN complex and implications for regulation of its assembly
    In: Nature Structural & Molecular Biology, Vol. 31, 2024, Nr. 6, pp. 861 – 873
    DOI (Open Access)
  • Musacchio, Andrea
    Thirty years of structural changes
    In: Nature Structural & Molecular Biology, Vol. 31, 2024, Nr. 1, pp. 4 – 5
    DOI
  • Cmentowski, Verena; Ciossani, Giuseppe; d'Amico, Ennio; Wohlgemuth, Sabine; Owa, Mikito; Dynlacht, Brian; Musacchio, Andrea
    RZZ‐Spindly and CENP‐E form an integrated platform to recruit dynein to the kinetochore corona
    In: The EMBO Journal, Vol. 42, 2023, Nr. 24, e114838
    DOI (Open Access)
  • d'Amico, Ennio A.; Ud Din Ahmad, Misbha; Cmentowski, Verena; Girbig, Mathias; Müller, Franziska; Wohlgemuth, Sabine; Brockmeyer, Andreas; Maffini, Stefano; Janning, Petra; Vetter, Ingrid R.; Carter, Andrew P.; Perrakis, Anastassis; Musacchio, Andrea
    Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin
    In: The Journal of Cell Biology (JCB), Vol. 221, 2022, Nr. 11, e202206131
    DOI (Open Access)
  • Musacchio, Andrea
    On the role of phase separation in the biogenesis of membraneless compartments
    In: The EMBO Journal, Vol. 41, 2022, Nr. 5, e109952
    DOI (Open Access)
  • Raisch, Tobias; Ciossani, Giuseppe; d’Amico, Ennio; Cmentowski, Verena; Carmignani, Sara; Maffini, Stefano; Merino, Felipe; Wohlgemuth, Sabine; Vetter, Ingrid R.; Raunser, Stefan; Musacchio, Andrea
    Structure of the RZZ complex and molecular basis of Spindly‐driven corona assembly at human kinetochores
    In: The EMBO Journal, Vol. 41, 2022, Nr. 9, e110411
    DOI, Online Full Text (Open Access)

    • Preprints

  • Pleuger, Richard; Cozma, Christian; Hohoff, Simone; Denkhaus, Christian; Dudziak, Alexander; Kaschani, Farnusch; Musacchio, Andrea; Vetter, Ingrid R.; Westermann, Stefan
    Ipl1-controlled attachment maturation regulates Mps1 association with its kinetochore receptor
    2023
    DOI (Open Access)

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