TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks

Alexandre Nore, Ariadna B. Juarez-Martinez, Julie Clément, Christine Brun, Boubou Diagouraga, Hamida Laroussi, Corinne Grey, Henri Marc Bourbon, Jan Kadlec (), Thomas Robert () and Bernard Massy ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34799-0

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