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Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation
Hamida Laroussi1, Ariadna B Juarez-Martinez1, Aline Le Roy1
1Université Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France.
The EMBO Journal
|July 11, 2023
Summary
Meiotic recombination relies on DNA double-strand breaks (DSBs) regulated by REC114, MEI4, and IHO1. This study reveals their complex interactions, suggesting REC114 acts as a regulatory hub for DSB formation and genome integrity.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Meiotic recombination initiates with DNA double-strand breaks (DSBs), crucial for genetic diversity and fertility.
- The TOPOVIL complex (SPO11/TOPOVIBL) catalyzes DSB formation in mice.
- REC114, MEI4, and IHO1 are key regulators of TOPOVIL activity, but their mechanisms remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which REC114, MEI4, and IHO1 regulate meiotic recombination.
- To characterize the structural assembly and interactions of these meiotic factors.
Main Methods:
- AlphaFold2 protein structure prediction.
- Biochemical characterization of protein complexes.
- Analysis of protein-protein interactions.
Main Results:
- Mouse REC114 forms homodimers; associates with MEI4 as a 2:1 heterotrimer, which then dimerizes.
- IHO1 forms stable tetramers via coiled-coil interactions.
- IHO1 directly binds the PH domain of REC114, competing with TOPOVIBL and ANKRD31 for the same binding surface.
- Evidence supports a ternary IHO1-REC114-MEI4 complex.
Conclusions:
- REC114 serves as a regulatory platform, mediating interactions with multiple partners.
- These findings provide mechanistic insights into the regulation of meiotic DSB formation.
- Understanding these interactions is vital for maintaining genome integrity during meiosis.
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