Conditional ablation experiments show that key components of the synaptonemal complex protect double Holliday junction recombination intermediates to ensure their resolution into crossover products, which are required for accurate chromosome segregation during meiosis.

A compact, AI-generated suppressor of DNA mismatch repair can enhance prime editing in vivo and in vitro and can be integrated into a variety of prime editing architectures.

Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossover...

In mitosis, sister chromatids are preferred repair templates for homologous recombination, whereas in meiosis interhomolog-based repair is promoted. How this switch, which is a defining event in sexua...

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The Mre11 nuclease, part of the conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs), is also essential to initiate meiotic recombination in budding yeast by promoting Spo11-induced DSBs. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM) that organize the meiotic DSB machinery by a mechanism involving biomolecular condensation. Here, we explored the role of Mre11 during meiosis and its relationship to RMM condensation. We show that both Mre11 and MRX complexes form DNA-dependent, hexanediol sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci in vegetative cells and DSB-independent foci in meiotic cells. In vitro condensates and in vivo foci both depend on the C-terminal intrinsically-disordered region (IDR) of Mre11. Importantly, while the Mre11 IDR is dispensable for vegetative DNA repair it is essential during meiosis. The C-terminus of Mre11 forms a short alpha-helix that binds a conserved region of Mer2, and mutating residues within this interface reduces Mre11 foci and DSB formation. Finally, we identified a SUMO-interacting motif within the Mre11 IDR that enhances recruitment of Mre11 during meiosis and facilitates DSB formation. This work identifies multiple mechanisms that collaborate to recruit Mre11 during meiosis to initiate recombination. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, 802525 Fonds National de la Recherche Scientifique, Bruxelles, BE, T.0031.22 Research Council VUB, SRP95, OZR3939 National Institute of Health, US, R01GM074223

Research Assistant / Research Associate (Fixed Term) in the Department of Plant Sciences at the University of Cambridge.

Genome instability is a hallmark of cancer cells but also a cause of genetic diseases in humans. Our understanding of the causal relationships between genome instability and the development of human d...

Reconstitution of recombinantly expressed SPO11–TOP6BL complex recapitulates its DNA cleavage function and together with structural modelling and biochemical experiments, provides insights into the re...

PRDM9 is a DNA-binding protein that helps determine the location of recombination hotspots in many mammals. This study of several species of salmonid fish reveals that PRDM9 function is conserved acro...

Research Laboratory Technician in the Department of Plant Sciences at the University of Cambridge.