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

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

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.

Citation

Skobelkina, A., Julien, M., Jeannin, S., Miron, S., Egger, T., Chaaban, R., Bouvignies, G., Alghoul, E., Ghouil, R., Friel, C., Busso, D., Cañas, J., Theillet, F.-X., Le Bars, R., Carreira, A., Constantinou, A., Basbous, J., & Zinn-Justin, S. (2025). KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis. Nucleic Acids Research, 53(11), Article gkaf476. https://doi.org/10.1093/nar/gkaf476

• Journal Article Type: Article
• Acceptance Date: May 21, 2025
• Online Publication Date: Jun 11, 2025
• Publication Date: 2025-06
• Deposit Date: Jun 20, 2025
• Publicly Available Date: Jun 20, 2025
• Journal: Nucleic Acids Research
• Print ISSN: 0305-1048
• Electronic ISSN: 1362-4962
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Issue: 11
• Article Number: gkaf476
• DOI: https://doi.org/10.1093/nar/gkaf476
• Public URL: https://nottingham-repository.worktribe.com/output/50438662
• Publisher URL: https://academic.oup.com/nar/article/53/11/gkaf476/8160319?login=false