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TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks

Author

Listed:
  • Alexandre Nore

    (Univ Montpellier)

  • Ariadna B. Juarez-Martinez

    (Univ. Grenoble Alpes, CNRS, CEA, IBS)

  • Julie Clément

    (Univ Montpellier)

  • Christine Brun

    (Univ Montpellier)

  • Boubou Diagouraga

    (CBS, Univ Montpellier, CNRS, INSERM)

  • Hamida Laroussi

    (Univ. Grenoble Alpes, CNRS, CEA, IBS)

  • Corinne Grey

    (Univ Montpellier)

  • Henri Marc Bourbon

    (Centre de Biologie Intégrative, CNRS, Université de Toulouse)

  • Jan Kadlec

    (Univ. Grenoble Alpes, CNRS, CEA, IBS)

  • Thomas Robert

    (CBS, Univ Montpellier, CNRS, INSERM)

  • Bernard Massy

    (Univ Montpellier)

Abstract

Meiosis requires the formation of programmed DNA double strand breaks (DSBs), essential for fertility and for generating genetic diversity. DSBs are induced by the catalytic activity of the TOPOVIL complex formed by SPO11 and TOPOVIBL. To ensure genomic integrity, DNA cleavage activity is tightly regulated, and several accessory factors (REC114, MEI4, IHO1, and MEI1) are needed for DSB formation in mice. How and when these proteins act is not understood. Here, we show that REC114 is a direct partner of TOPOVIBL, and identify their conserved interacting domains by structural analysis. We then analyse the role of this interaction by monitoring meiotic DSBs in female and male mice carrying point mutations in TOPOVIBL that decrease or disrupt its binding to REC114. In these mutants, DSB activity is strongly reduced genome-wide in oocytes, and only in sub-telomeric regions in spermatocytes. In addition, in mutant spermatocytes, DSB activity is delayed in autosomes. These results suggest that REC114 is a key member of the TOPOVIL catalytic complex, and that the REC114/TOPOVIBL interaction ensures the efficiency and timing of DSB activity.

Suggested Citation

  • Alexandre Nore & Ariadna B. Juarez-Martinez & Julie Clément & Christine Brun & Boubou Diagouraga & Hamida Laroussi & Corinne Grey & Henri Marc Bourbon & Jan Kadlec & Thomas Robert & Bernard Massy, 2022. "TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34799-0
    DOI: 10.1038/s41467-022-34799-0
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    References listed on IDEAS

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