Evolutionary conservation of the structure and function of meiotic Rec114−Mei4 and Mer2 complexes
(2023) Genes & Development — Vol. 37, n° 11-12, p. 535-553 (2023)
Files
Pre-Print.pdf
Open Access - Adobe PDF
- 7.46 MB
Details
- Authors
- 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 AlphaFold structures 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 co-aligned DNA duplexes, likely through extensive electrostatic interactions along the length of the coiled coil. Finally, we show that the structure 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 where Mer2 condensation is the essential driver of assembly, with the DNAbinding activity of Rec114-Mei4 playing a supportive role.
- Affiliations
Citations
Daccache, D., De Jonge, E., Liloku, P., Mechleb, K., Haddad, M., Corthaut, S., Sterckx, Y. G.-J., Volkov, A. N., & Claeys Bouuaert, C. (2023). Evolutionary conservation of the structure and function of meiotic Rec114−Mei4 and Mer2 complexes. Genes & Development, 37(11-12), 535-553. https://doi.org/10.1101/gad.350462.123 (Original work published 2023)