Evolutionary conservation of the structure and function of meiotic Rec114-Mei4 and Mer2 complexes [Research Papers]

Meiosis-specific Rec114–Mei4 and Mer2 complexes are thought to enable Spo11-mediated DNA double-strand break (DSB) formation through a mechanism that involves DNA-dependent condensation. However, the structure, molecular properties, and evolutionary conservation of Rec114–Mei4 and Mer2 are unclear. Here, we present AlphaFold models of Rec114–Mei4 and Mer2 complexes supported by nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), and mutagenesis. We show that dimers composed of the Rec114 C terminus form α-helical chains that cup an N-terminal Mei4 α helix, and that Mer2 forms a parallel homotetrameric coiled coil. Both Rec114–Mei4 and Mer2 bind preferentially to branched DNA substrates, indicative of multivalent protein–DNA interactions. Indeed, the Rec114–Mei4 interaction domain contains two DNA-binding sites that point in opposite directions and drive condensation. The Mer2 coiled-coil domain bridges coaligned DNA duplexes, likely through extensive electrostatic interactions along the length of the coiled coil. Finally, we show that the structures of Rec114–Mei4 and Mer2 are conserved across eukaryotes, while DNA-binding properties vary significantly. This work provides insights into the mechanism whereby Rec114–Mei4 and Mer2 complexes promote the assembly of the meiotic DSB machinery and suggests a model in which Mer2 condensation is the essential driver of assembly, with the DNA-bi...

Source: Genes and Development - July 18, 2023 Category: Genetics & Stem Cells Authors: Daccache, D., De Jonge, E., Liloku, P., Mechleb, K., Haddad, M., Corthaut, S., Sterckx, Y. G.- J., Volkov, A. N., Claeys Bouuaert, C. Tags: Research Papers Source Type: research