KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis

Year: 2025

Type: article

Abstract: During mitosis, the microtubule depolymerase KIF2C, the tumor suppressor BRCA2, and the kinase PLK1 contribute to the control of kinetochore-microtubule attachments. Both KIF2C and BRCA2 are phosphorylated by PLK1, and BRCA2 phosphorylated at T207 (BRCA2-pT207) serves as a docking site for PLK1. Reducing this interaction results in unstable microtubule-kinetochore attachments. Here we identified that KIF2C also directly interacts with BRCA2-pT207. Indeed, the N-terminal domain of KIF2C adopts a Tudor/PWWP/MBT fold that unexpectedly binds to phosphorylated motifs. Using an optogenetic platform, we found that KIF2C forms membrane-less organelles that assemble through interactions mediated by this phospho-binding domain. KIF2C condensation does not depend on BRCA2-pT207 but requires active Aurora B and PLK1 kinases. Moreover, it concentrates PLK1 and BRCA2-pT207 in an Aurora B-dependent manner. Finally, KIF2C depolymerase activity promotes the formation of KIF2C condensates, but strikingly, KIF2C condensates exclude tubulin: they are located on microtubules, especially at their extremities. Altogether, our results suggest that, during the attachment of kinetochores to microtubules, the assembly of KIF2C condensates amplifies PLK1 and KIF2C catalytic activities and spatially concentrates BRCA2-pT207 at the extremities of microtubules. We propose that this novel and highly regulated mechanism contributes to the control of microtubule-kinetochore attachments, chromosome alignment, and stability.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf476

Authors: Anastasiia Skobelkina, Manon Julien, Sylvain Jeannin, Simona Miron, Tom Egger, Rady Chaaban, Guillaume Bouvignies, Emile Alghoul, Rania Ghouil, Claire Friel, Didier Busso, Juan C Cañas, François-Xavier Theillet, Romain Le Bars, Aura Carreira, Angelos Constantinou, Jihane Basbous, Sophie Zinn-Justin

Institutions: Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut de Biologie Intégrative de la Cellule, Université de Montpellier, Institut de Génétique Humaine, Université Paris Sciences et Lettres, Intégrité du génome, ARN et cancer, Centro de Biología Molecular Severo Ochoa, Institut Curie, École Normale Supérieure - PSL, Sorbonne Université, Laboratoire des Biomolécules, University of Nottingham, Queen's Medical Centre, Inserm, Université Paris Cité, CEA Paris-Saclay - Etablissement de Fontenay-aux-roses, Stabilité Génétique, Cellules Souches et Radiations

Language: English

Topic: Microtubule and mitosis dynamics

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,992

Funders: Biogen, California Earthquake Authority, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique, Institut National Du Cancer, French Infrastructure for Integrated Structural Biology, College of Natural Resources and Sciences, Humboldt State University, National Cancer Institute, Division of Arctic Sciences, Vermont Agency of Natural Resources

OpenAlex ID: W4411209503