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Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1

Author

Listed:
  • Åsa Ehlén

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

  • Charlotte Martin

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

  • Simona Miron

    (CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay)

  • Manon Julien

    (CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay
    École Normale Supérieure)

  • François-Xavier Theillet

    (CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay)

  • Virginie Ropars

    (CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay)

  • Gaetana Sessa

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

  • Romane Beaurepere

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

  • Virginie Boucherit

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

  • Patricia Duchambon

    (Institut Curie
    INSERM U1196)

  • Ahmed El Marjou

    (Institut Curie
    CNRS UMR144)

  • Sophie Zinn-Justin

    (CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay)

  • Aura Carreira

    (PSL Research University, CNRS, UMR3348
    Paris Sud University, Paris-Saclay University CNRS, UMR3348)

Abstract

The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identify a conserved phosphorylation site at T207 of BRCA2 that constitutes a bona fide docking site for PLK1 and is phosphorylated in mitotic cells. We show that BRCA2 bound to PLK1 forms a complex with the phosphatase PP2A and phosphorylated-BUBR1. Reducing BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants S206C and T207A, alters the tetrameric complex resulting in unstable kinetochore-microtubule interactions, misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a role of BRCA2 in the alignment of chromosomes, distinct from its DNA repair function, with important consequences on chromosome stability. These findings may explain in part the aneuploidy observed in BRCA2-mutated tumors.

Suggested Citation

  • Åsa Ehlén & Charlotte Martin & Simona Miron & Manon Julien & François-Xavier Theillet & Virginie Ropars & Gaetana Sessa & Romane Beaurepere & Virginie Boucherit & Patricia Duchambon & Ahmed El Marjou , 2020. "Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1," Nature Communications, Nature, vol. 11(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15689-9
    DOI: 10.1038/s41467-020-15689-9
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    Cited by:

    1. Domagoj Vugic & Isaac Dumoulin & Charlotte Martin & Anna Minello & Lucia Alvaro-Aranda & Jesus Gomez-Escudero & Rady Chaaban & Rana Lebdy & Catharina Nicolai & Virginie Boucherit & Cyril Ribeyre & Ang, 2023. "Replication gap suppression depends on the double-strand DNA binding activity of BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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