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 homologous recombination. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2, proposed to organize the DSB machinery via biomolecular 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 dispensable 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.
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Data availability
The NMR data generated in this study have been deposited in the Biological Magnetic Resonance Bank with the accession number 53209. Accession codes for protein structures used for AlphaFold models are listed below: AF-P32829-F1, CAA60944, BAA02017, XP_003669210.1 [https://www.ncbi.nlm.nih.gov/protein/XP_003669210.1], XP_003672532.1 [https://www.ncbi.nlm.nih.gov/protein/XP_003672532.1], XP_001647040.1 [https://www.ncbi.nlm.nih.gov/protein/XP_001647040.1], XP_001642997.1 [https://www.ncbi.nlm.nih.gov/protein/XP_001642997.1], XP_003683996.1 [https://www.ncbi.nlm.nih.gov/protein/XP_003683996.1], XP_003686402.1 [https://www.ncbi.nlm.nih.gov/protein/XP_003686402.1] and AF-Q12306-F1. AlphaFold models are available in ModelArchive (modelarchive.org) with the following accession codes: ma-bjxr0 [https://modelarchive.org/doi/10.5452/ma-bjxr0], ma-sljg3 [https://modelarchive.org/doi/10.5452/ma-sljg3], ma-byd98 [https://modelarchive.org/doi/10.5452/ma-byd98], ma-itjlc [https://modelarchive.org/doi/10.5452/ma-itjlc] and ma-b9r3g. Source data are provided in this paper.
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Acknowledgements
We thank David Alvarez Melo for generating Mer2-iV5 tagged strains, John Weir for plasmids and strains, and C.C.B. laboratory members for discussion. We thank the Biological Imaging facility (IMABIOL) at UCLouvain and Marie-Christine Eloy for providing training in the use of the epifluorescence microscope. This work was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement 802525 to C.C.B.), and the Fonds National de la Recherche Scientifique (PDR grant T.0031.22 to C.C.B.). P.P. is funded by FNRS Aspirant fellowships (project 1.A908.22). C.C.B. is an FNRS Research Associate. W.E.Y.M. and S.B. acknowledge the Research Council of VUB for support through the Strategic Research Program SRP95 and the infrastructure grant OZR3939. NIH NIGMS grant R01GM074223 supported NH, who is also an Investigator of the Howard Hughes Medical Institute.
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P.P. designed, executed, and analyzed all experiments except as noted; M.S. performed Southern blot experiments; W.E.Y.M. synthesized peptides under the supervision of S.B., performed ITC experiments and analyzed NMR data; A.N.V. acquired and analyzed NMR data; R.B. performed yeast 2-hybrid experiments under the supervision of N.H.; C.C.B. supervised the research and secured funding. P.P. and C.C.B wrote the paper with input from all authors.
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Priyadarshini, P., Survi, M., El Yazidi Mouloud, W. et al. Recruitment of Mre11 to recombination sites during meiosis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71310-5
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DOI: https://doi.org/10.1038/s41467-026-71310-5
