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PreprintCited by 2DNA Repair MechanismsFungal and yeast genetics researchGenomics and Chromatin Dynamics

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Recruitment of Mre11 to recombination sites during meiosis

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Bouuaert, Corentin Claeys, Priyadarshini, Priyanka, Survi, Mahesh, Mouloud, Wael El Yazidi, Bohn, Regina, Ballet, Steven, Hunter, Neil, Volkov, Alexander·2025·Nature Communications
DOI 10.21203/rs.3.rs-7215871/v1PMC PMC12265730

Preprint — published as 10.1038/s41467-026-71310-5

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Abstract

The Mre11 nuclease is part of the highly conserved MRX complex involved in the repair of DNA double-strand breaks (DSBs). During meiosis in budding yeast, MRX is also required for the programmed induction of DSBs by Spo11, thereby initiating homologous recombination to promote accurate chromosome segregation. Recruitment of Mre11 to meiotic DSB sites depends on Rec114-Mei4 and Mer2 (RMM), which are thought to 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-terminal region of Mre11 forms a short α-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. Our results provide new insights into the biophysical properties of Mre11 and its role in initiating meiotic recombination.

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Metadata

Authors
Bouuaert, C. C., Priyadarshini, P., Survi, M., Mouloud, W. E. Y., Bohn, R., Ballet, S., Hunter, N., & Volkov, A.
Affiliations
  • UCLouvain (BE)
  • Vrije Universiteit Brussel (BE)
  • Howard Hughes Medical Institute / UC Davis
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Bouuaert, Corentin Claeys
  • Priyadarshini, Priyanka
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2025-08-19
Volume
17
Issue
1
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-7215871/v1
PMC
PMC12265730
OpenAlex
W4412172758
Cited by
2
References
1
Citations by year
2026: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Université Catholique de Louvain
  • European Commission (HORIZON2020)
  • Fonds De La Recherche Scientifique - FNRS
  • Vrije Universiteit Brussel
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM074223)
  • H2020 European Research Council (802525)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
MRE11, MRX complex, meiotic recombination, DNA double-strand break repair, Spo11, biomolecular condensates, intrinsically disordered regions, SUMO-interacting motif, DNA damage foci, Saccharomyces cerevisiae

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