TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks
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Abstract
Meiosis requires the formation of programmed DNA double strand breaks (DSBs), essential for fertility and for generating genetic diversity. DSBs are induced by the catalytic activity of the TOPOVIL complex formed by SPO11 and TOPOVIBL. To ensure genomic integrity, DNA cleavage activity is tightly regulated, and several accessory factors (REC114, MEI4, IHO1, and MEI1) are needed for DSB formation in mice. How and when these proteins act is not understood. Here, we show that REC114 is a direct partner of TOPOVIBL, and identify their conserved interacting domains by structural analysis. We then analyse the role of this interaction by monitoring meiotic DSBs in female and male mice carrying point mutations in TOPOVIBL that decrease or disrupt its binding to REC114. In these mutants, DSB activity is strongly reduced genome-wide in oocytes, and only in sub-telomeric regions in spermatocytes. In addition, in mutant spermatocytes, DSB activity is delayed in autosomes. These results suggest that REC114 is a key member of the TOPOVIL catalytic complex, and that the REC114/TOPOVIBL interaction ensures the efficiency and timing of DSB activity.
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Highly accurate protein structure prediction with AlphaFold
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Genetic recombination is directed away from functional genomic elements in mice
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Phosphoregulation of DSB-1 mediates control of meiotic double-strand break activity
Guo, H., Stamper, E. L., Sato-Carlton, A., Shimazoe, M. A., Li, X., Zhang, L., Stevens, L., Tam, K. J., Dernburg, A. F., & Carlton, P. M. (2022) · eLife · doi:10.7554/elife.77956 · Cited by 32 · see citing works
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- Authors
- Nore, A., Juarez-Martinez, A. B., Clément, J., Brun, C., Diagouraga, B., Laroussi, H., Grey, C., Bourbon, H. M., Kadlec, J., Robert, T., & de Massy, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kadlec, Jan
- Robert, Thomas
- ORCID
- Venue
- Nature Communications
- Published
- 2022-11-17
- Volume
- 13
- Issue
- 1
- Pages
- 7048-7048
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9671922
- OpenAlex
- W4309235947
- Cited by
- 43
- References
- 3
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 12 · 2022: 3
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- ANR
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- REC114, meiotic DNA double-strand breaks, Spo11, meiotic recombination, protein-protein interaction, protein structure, oocytes, spermatocytes, subtelomeric regions
- MeSH terms
- Animals, Chromosomes, DNA, Female, Male, Meiosis, Spermatocytes, Mice, DNA Breaks, Double-Stranded
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