Evolutionary conservation of the structure and function of meiotic Rec114–Mei4 and Mer2 complexes

Abstract

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 structures of Rec114–Mei4 and Mer2 complexes, supported by AlphaFold modeling, nuclear magnetic resonance (NMR) spectroscopy, crosslinking-mass spectrometry (XL-MS), 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 independent DNA-binding sites that point in opposite directions and likely drive condensation. In addition, Mer2 binds efficiently to nucleosomesin vitro, while Rec114–Mei4 does not. Finally, we show that the structure and properties of Rec114–Mei4 and Mer2 are conserved across eukaryotes. This work provides insights into the molecular mechanism whereby Rec114–Mei4 and Mer2 complexes promote the assembly of the meiotic DSB machinery.