Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4

Author:

Kumar Rajeev1,Oliver Cecilia2,Brun Christine2,Juarez-Martinez Ariadna B3,Tarabay Yara2,Kadlec Jan3,de Massy Bernard2ORCID

Affiliation:

1. Institut Jean-Pierre Bourgin, Unité Mixte de Recherche 1318 Institut National de la Recherche Agronomique-AgroParisTech, Université Paris-Saclay, Versailles, France

2. Institut de Génétique Humaine, Centre National de la Recherche Scientifique (CNRS), Université de Montpellier, Montpellier, France

3. Institut de Biologie Structurale, Université Grenoble Alpes, Commissariat à l'Energie Atomique et aux Energies Alternatives, CNRS, Grenoble, France

Abstract

Programmed formation of DNA double-strand breaks (DSBs) initiates the meiotic homologous recombination pathway. This pathway is essential for proper chromosome segregation at the first meiotic division and fertility. Meiotic DSBs are catalyzed by Spo11. Several other proteins are essential for meiotic DSB formation, including three evolutionarily conserved proteins first identified in Saccharomyces cerevisiae (Mer2, Mei4, and Rec114). These three S. cerevisiae proteins and their mouse orthologs (IHO1, MEI4, and REC114) co-localize on the axes of meiotic chromosomes, and mouse IHO1 and MEI4 are essential for meiotic DSB formation. Here, we show that mouse Rec114 is required for meiotic DSB formation. Moreover, MEI4 forms a complex with REC114 and IHO1 in mouse spermatocytes, consistent with cytological observations. We then demonstrated in vitro the formation of a stable complex between REC114 C-terminal domain and MEI4 N-terminal domain. We further determine the structure of the REC114 N-terminal domain that revealed similarity with Pleckstrin homology domains. These analyses provide direct insights into the architecture of these essential components of the meiotic DSB machinery.

Funder

Akira Shinohara and Osaka University

Labex GRAL

FRISBI

GRAL

Centre National pour la Recherche Scientifique

European Research Council

LabexEpigenMed

Fondation Bettencourt-Schueller

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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