The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Characterization of the REC114-MEI4-IHO1 complex regulating meiotic DNA double-strand break formation
Open accessPreprint — published as 10.15252/embj.2023113866 · Paper page
Abstract
Meiotic recombination is initiated by the formation of DNA double-strand breaks (DSBs), essential for fertility and genetic diversity. In the mouse, DSBs are formed by the catalytic TOPOVIL complex consisting of SPO11 and TOPOVIBL. To preserve genome integrity, the activity of the TOPOVIL complex is finely controlled by several meiotic factors including REC114, MEI4 and IHO1, but the underlying mechanism is poorly understood. Here, we report that mouse REC114 forms homodimers, that it associates with MEI4 as a 2:1 heterotrimer that further dimerizes, and that IHO1 forms coiled-coil based tetramers. Using AlphaFold2 modelling combined with biochemical characterization we uncovered the molecular details of these assemblies. Finally, we show that IHO1 directly interacts with the PH domain of REC114 by recognizing the same surface as TOPOVIBL and another meiotic factor ANKRD31. These results provide strong evidence for the existence of a ternary IHO1-REC114-MEI4 complex and show that REC114 is a potential regulatory platform mediating mutually exclusive interactions with several partners.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 37
- 2020, Ensuring meiotic DNA break formation in the mouse pseudoautosomal region, Nature, 582, 426, 10.1038/s41586-020-2327-4 · DOI
- 10.1016/S1097-2765(04)00063-2 · DOI · Paper page
- 10.1038/nrg3573 · DOI
- 10.1016/S1097-2765(00)00098-8 · DOI
- 10.1016/j.molcel.2019.03.023 · DOI
- 10.1007/978-1-4939-7759-8_9 · DOI
- 2020, Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry, J. Proteomics, 222, 103799, 10.1016/j.jprot.2020.103799 · DOI
- 10.1016/bs.mie.2015.05.001 · DOI
- 2022, Evolution and Diversity of the TopoVI and TopoVI-like Subunits With Extensive Divergence of the TOPOVIBL subunit, Mol. Biol. Evol, 39, msac227, 10.1093/molbev/msac227 · DOI
- 2021, DNA-driven condensation assembles the meiotic DNA break machinery, Nature, 592, 144, 10.1038/s41586-021-03374-w · DOI
- 2021, Structural and functional characterization of the Spo11 core complex, Nat. Struct. Mol. Biol, 28, 92, 10.1038/s41594-020-00534-w · DOI · Paper page
- 10.1146/annurev-genet-110711-155423 · DOI
- 2021, Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice, Nucleic Acids Res, 49, 2609, 10.1093/nar/gkab082 · DOI
- 10.1016/j.cell.2006.04.039 · DOI
- 10.1101/cshperspect.a016618 · DOI
- 10.1128/MCB.23.16.5928-5938.2003 · DOI
- 10.1101/gad.571710 · DOI
- 10.1242/jcs.165464 · DOI
- 10.26508/lsa.201800259 · DOI
- 10.1101/cshperspect.a016634 · DOI
- 10.1007/s00412-007-0111-y · DOI
- 10.1021/acs.analchem.5b00140 · DOI · Paper page
- 10.1021/ac300056a · DOI
- 2022, TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks, Nat. Commun, 13, 7048, 10.1038/s41467-022-34799-0 · DOI · Paper page
- 10.1016/j.cell.2011.07.003 · DOI
- 10.1016/j.molcel.2019.03.022 · DOI
- 2020, A Guide to Native Mass Spectrometry to determine complex interactomes of molecular machines, FEBS J, 287, 2428, 10.1111/febs.15281 · DOI
- 10.1007/s00412-005-0346-4 · DOI
- 10.1126/science.aad5309 · DOI · Paper page
- 10.1016/S1097-2765(00)00097-6 · DOI
- 2021, Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation, Elife, 10, e72330, 10.7554/eLife.72330 · DOI
- 10.1101/gad.1626608 · DOI
- 10.1016/S0006-3495(00)76713-0 · DOI
- 10.1038/ncb3417 · DOI
- 10.1101/gad.304543.117 · DOI
- 10.3389/fgene.2018.00521 · DOI
- 2021, Mechanism and Control of Meiotic DNA Double-Strand Break Formation in S, cerevisiae. Front. Cell Dev. Biol, 9, 642737, 10.3389/fcell.2021.642737 · DOI
Metadata
- Authors
- Laroussi, H., Juarez-Martinez, A. B., Roy, A. L., Erba, E. B., de Massy, B., & Kadlec, J.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kadlec, Jan
- Venue
- The EMBO Journal
- Publisher
- openRxiv
- Published
- 2023-01-11
- Volume
- 42
- Issue
- 16
- Pages
- e113866-e113866
- ISSN
- 0261-4189 (ISSN-L)
- PMC
- PMC10425845
- OpenAlex
- W4383873224
- Cited by
- 22
- References
- 1
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 4
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- European Commission (ANR-17-EURE-0003, 2007–2013, UAR 3518 CNRS-CEA-UGA-EMBL, FP7 2007-2013, HORIZON2020, 609102, FP7/2007)
- Agence Nationale de la Recherche (UAR 3518 CNRS-CEA-UGA-EMBL, ANR-17-EURE-0003, ANR-17-EURE-, 0024-01, ANR18, ANR-18-CE11, ANR-18-CE11-0024, ANR-17, ANR-10, ANR-10-LABX-49-01, ANR-10-INBS-0005, ANR-10-LABX-0049)
- European Synchrotron Radiation Facility
- Centre National de la Recherche Scientifique (Fr3050, ANR‐17‐EURE‐0003, ANR-18-CE11, UAR 3518 CNRS-CEA-UGA-EMBL)
- Campus France (PCOFUND‐GA‐2013‐609102)
- French Infrastructure for Integrated Structural Biology (ANR-17-EURE-0003, ANR-10-INBS-0005, ANR-10-INBS-000502, ANR-10-INBS, ANR-10-LABX-49-01)
- College of Natural Resources and Sciences, Humboldt State University (IR‐RMN‐THC Fr3050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- REC114, MEI4, meiotic recombination, Spo11, protein complex formation, protein dimerization, pleckstrin homology domain, protein-protein interaction
- MeSH terms
- Animals, DNA, Meiosis, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases, Mice, Homologous Recombination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
