Characterization of the REC114‐MEI4‐IHO1 complex regulating meiotic DNA double‐strand break formation - Groupe Extremophiles et grands assemblages moléculaires / Extremophiles and Large Molecular Assemblies Group (IBS-ELMA) Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2023

Characterization of the REC114‐MEI4‐IHO1 complex regulating meiotic DNA double‐strand break formation

Frank Gabel
Bernard de Massy
Jan Kadlec

Résumé

Meiotic recombination is initiated by the formation of DNA double‐strand breaks (DSBs), essential for fertility and genetic diversity. In the mouse, DSBs are formed by the catalytic TOPOVIL complex consisting of SPO11 and TOPOVIBL. To preserve genome integrity, the activity of the TOPOVIL complex is finely controlled by several meiotic factors including REC114, MEI4, and IHO1, but the underlying mechanism is poorly understood. Here, we report that mouse REC114 forms homodimers, that it associates with MEI4 as a 2:1 heterotrimer that further dimerizes, and that IHO1 forms coiled‐coil‐based tetramers. Using AlphaFold2 modeling combined with biochemical characterization, we uncovered the molecular details of these assemblies. Finally, we show that IHO1 directly interacts with the PH domain of REC114 by recognizing the same surface as TOPOVIBL and another meiotic factor ANKRD31. These results provide strong evidence for the existence of a ternary IHO1‐REC114‐MEI4 complex and suggest that REC114 could act as a potential regulatory platform mediating mutually exclusive interactions with several partners.
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Dates et versions

hal-04199701 , version 1 (23-11-2023)

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Hamida Laroussi, Ariadna Juarez-Martinez, Aline Le Roy, Elisabetta Boeri Erba, Frank Gabel, et al.. Characterization of the REC114‐MEI4‐IHO1 complex regulating meiotic DNA double‐strand break formation. EMBO Journal, 2023, 42 (16), pp.e113866. ⟨10.15252/embj.2023113866⟩. ⟨hal-04199701⟩
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