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

• DOI: 10.15252/embj.2023113866
• Publication Date: 2023-07-11T11:58:10Z
• Authors: Hamida Laroussi; Ariadna B Juarez‐...; Aline Le Roy; Elisabetta Boeri ...; Frank Gabel; Bernard de Massy; Jan Kadlec
• Keywords: Ternary complex; Characterization

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