Recruitment of Mre11 to recombination sites during meiosis
(2026) Nature Communications — Vol. 17, n° 1 (2026)
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Priyadarshini, Priyanka 
- Abstract
- The Mre11 nuclease is part of the conserved MRX complex involved in DNA double-strand break (DSB) repair. During meiosis in budding yeast, MRX is also required for Spo11-mediated programmed DSB formation to initiate homo-logous recombination. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2, proposed to organize the DSB machinery via biomo-lecular condensation. Here, we show that Mre11 and MRX complexes form DNA-dependent, hexanediol-sensitive condensates in vitro. In vivo, Mre11 assembles into DNA damage-dependent foci during mitosis and DSB-independent foci during meiosis. Both in vitro condensates and in vivo foci require Mre11 C-terminal intrinsically-disordered region (IDR). While dis-pensable for vegetative DNA repair, Mre11 IDR is essential during meiosis, where it mediates interaction with Mer2 via a short α-helix and contains a SUMO-interacting motif that enhances Mre11 recruitment and DSB formation. Together, these findings provide insights into the biophysical properties of Mre11 and its role in initiating meiotic recombination. Cells continuously experience exogenous and endogenous stress, leading to cytotoxic lesions such as DNA double-strand breaks (DSBs) 1,2. If not repaired promptly and accurately, DSBs can compromise genome stability, resulting in cellular dysfunction, tumorigenesis, or cell death 3. While DSBs are generally considered detrimental for genome integrity, several instances of programmed DSBs that serve a physiological purpose are also well-documented, including V(D)J recombination during lymphocyte development, immunoglobulin class-switching, and meiotic recombination 4. During meiosis, recombination initiated by programmed DNA DSBs serves two critical functions: it ensures accurate segregation of genetic material by forming physical connections between homologous chromosomes and increases genetic diversity through allelic shuffling 5,6. Meiotic DSBs are generated by the highly conserved type II topoisomerase-like protein Spo11 that acts in a consortium with several accessory factors, referred to as DSB proteins 7,8. In Saccharomyces cerevisiae, the nine known DSB proteins include Rec114-Mei4 and Mer2 (RMM). These are proposed to assemble into nucleoprotein condensates along meiotic chromosomes 9 that act as sub-cellular compartments that recruit other DSB proteins to stimulate DNA cleavage by controlling Spo11 dimerization 10-14. This condensation model provides a mechanism that ties DSB formation to the loop-axis organization of meiotic chromosomes 15,16. DSB formation in S. cerevisiae also depends on the Mre11-Rad50-Xrs2 (MRX) complex 17-20. In addition, MRX initiates the resection of DSB ends in both meiotic and mitotically cycling cells, through the endonuclease and exonuclease activities of Mre11 21-27. Further, the MRX complex has notable roles in telomere maintenance, stabilization of replication forks, and viral infection 28-30 .
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Citations
Priyadarshini, P., Survi, M., El Yazidi Mouloud, W., Bohn, R., Ballet, S., Hunter, N., Volkov, A., & Claeys Bouuaert, C. (2026). Recruitment of Mre11 to recombination sites during meiosis. Nature Communications, 17(1). https://doi.org/10.1038/s41467-026-71310-5 (Original work published 2026)