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. Red...

ver descrição completa

Detalhes bibliográficos
Autores: 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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/417416
Acesso em linha:http://hdl.handle.net/10261/417416
Access Level:acceso abierto
id ES_b5fbba5095f662299f4c430bbd0804eb
oai_identifier_str oai:digital.csic.es:10261/417416
network_acronym_str ES
network_name_str España
repository_id_str
spelling KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosisSkobelkina, AnastasiiaJulien, ManonJeannin, SylvainMiron, SimonaEgger, TomChaaban, RadyBouvignies, GuillaumeAlghoul, EmileGhouil, RaniaFriel, ClaireBusso, DidierCañas, Juan CTheillet, François-XavierLe Bars, RomainCarreira, AuraConstantinou, AngelosBasbous, JihaneZinn-Justin, SophieDuring 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.This work was supported by the CNRS and the CEA-Saclay, by the French Infrastructure for Integrated Structural Biology (https://frisbi.eu/, grant number ANR-10-INSB-05-01, Acronym FRISBI), by INSERM (PCSI 2022 grant BRCAPS coordinated by S.Z.J.), by ANR (grant number ANR-21-CEA13-0030 coordinated by Au.C.) and by ARC (ARC 2021 PJA3 grant N°248989 coordinated by S.Z.J.). A.S. was funded by the CEA, Synchrotron SOLEIL, and FRM (grant N°FDT202304016927). R.C. was supported by a PSL University Fellowship. J.C.C. was supported by a grant from Asociacion Española contra el Cancer (AECC) PRYGN234480CARR to Au.C. The Constantinou lab was supported by the French National Cancer Institute INCa (PLBIO 2021), by the French Agence Nationale de la Recherche ANR (AAPG2021 and AAPG2023), and by the Fondation MSD AVENIR. The present work has benefited from Imagerie‐Gif core facility supported by I’Agence Nationale de la Recherche (FBI ANR-24-INBS-0005 (BIOGEN); SPS ANR-17-EUR-0007, EUR SPS-GSR). Financial support from the IR INFRANALYTICS FR2054 for conducting the research is also gratefully acknowledged.Oxford University PressAsociación Española Contra el CáncerMSD AvenirConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2026202620252026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/417416reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AECC/PRYGN234480CARR/http://dx.doi.org/10.1093/nar/gkaf476Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4174162026-05-22T06:33:51Z
dc.title.none.fl_str_mv KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
title KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
spellingShingle KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
Skobelkina, Anastasiia
title_short KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
title_full KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
title_fullStr KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
title_full_unstemmed KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
title_sort KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis
dc.creator.none.fl_str_mv 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
author Skobelkina, Anastasiia
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Asociación Española Contra el Cáncer
MSD Avenir
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description 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.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/417416
url http://hdl.handle.net/10261/417416
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AECC/PRYGN234480CARR/
http://dx.doi.org/10.1093/nar/gkaf476
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417408336232448
score 15,812429

Registos relacionados