Characterization of a key meiosis regulatory complex

During meiosis, the formation of DNA double-strand breaks by the catalytic complex SPO11/TOPOVIBL and their repair through meiotic recombination are crucial mechanisms for the precise segregation of homologous chromosomes and the formation of gametes. However, the formation of these breaks can be dangerous and lead to undesirable chromosomal rearrangements if they are not introduced at the appropriate time and repaired correctly. Therefore, the activity of the SPO11-TOPOVIBL complex is tightly controlled and depends on several protein factors, such as the REC114-MEI4 complex and the IHO1 protein. Despite their importance during meiosis, little information was available regarding the biochemical properties of these protein factors and the molecular mechanism of their action.

In this study, researchers from the EPIGEN group and their collaborators reveal that the mouse protein IHO1 interacts with the REC114 protein, forming a stable ternary complex (REC114-MEI4-IHO1). By combining biochemical and biophysical analyses with AlphaFold2 modeling, they propose a model of the organization of this complex with a stoichiometry of 4IHO1:4REC114:2MEI4 and uncover the molecular details of this assembly. Furthermore, this work suggests that the binding of IHO1 to REC114 is mutually exclusive with that of TOPOVIBL and another meiotic factor ANKRD31. This suggests that REC114 may play a role of a platform in the regulation of meiotic DNA double-strand break formation.

Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation. Laroussi H, Juarez-Martinez AB, Le Roy A, Boeri Erba E, de Massy B, Kadlec K. EMBO Journal 2023 ; e113866. doi : 10.15252/embj.2023113866.

Contact : Jan Kadlec (IBS/Epigenetics and molecular pathways Group)