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

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.

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Publication Details

Journal
Nucleic Acids Research
Published
2025-06-06
DOI
https://doi.org/10.1093/nar/gkaf476
Citations
1
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
1.15

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article

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

Jihane Basbous, Romain Le Bars, Simona Miron, Rady Chaaban et al.
1 citations
Nucleic Acids Research
Microtubule and mitosis dynamics
1.15
article

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

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

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.

Nucleic Acids ResearchVol. 53(11)
Centre National de la Recherche Scientifique (FR), University of Nottingham (GB), Inserm (FR), Université de Montpellier (FR), Université Paris Cité (FR), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), École Normale Supérieure - PSL (FR), Sorbonne Université (FR), Institut de Biologie Intégrative de la Cellule (FR), CEA Paris-Saclay (FR), Centro de Biología Molecular Severo Ochoa (ES), Laboratoire des Biomolécules (FR), Universidad Autónoma de Madrid (ES), Institut Curie (FR)
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
Openalex Percentile: Top 23%
Microtubule and mitosis dynamics
1.15
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