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Recombinational DNA double-strand breaks in mice precede synapsis

Nature Genetics volume 27, pages 271–276 (2001)Cite this article

Abstract

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (γ-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of γ-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.

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Figure 1: Expression of γ-H2AX in the testis.
Figure 2: Expression of γ-H2AX during XY male meiosis.
Figure 3: Expression of γ-H2AX in spermatogenic cells from Spo11−/− and Msh5−/− mice.
Figure 4: Karyotype (a–c) and expression of γ-H2AX (d–f) in T(1;13)70H/T(1;13)Wa double translocation heterozygotes.
Figure 5: The relationship between γ-H2AX domains, axial elements and DMC1 foci during leptotene and zygotene.

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Acknowledgements

We thank H.-J. Garchon for the anti-XLR antibody; P. Moens and B. Spyropoulos for the anti-COR1 and anti-SYN1 antibodies; A. Davies, J.-Y. Masson and S. West for the anti-DMC1 antibody; R. Benavente for the anti-SCP3 antibody; W. Earnshaw for the CREST antibody; H. te Riele for providing Msh5−/− mice; S. Pagakis for help with imaging; and Á. Rattigan and O. Ojarikre for help with mouse genotyping and breeding.

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Authors and Affiliations

  1. Division of Developmental Genetics, National Institute for Medical Research, London, UK

    Shantha K. Mahadevaiah, James M.A. Turner & Paul S. Burgoyne

  2. Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Frédéric Baudat, Maria Jasin & Scott Keeney

  3. Laboratory of Molecular Pharmacology, NCI, National Institutes of Health, Bethesda, Maryland, USA

    Emmy P. Rogakou & William M. Bonner

  4. Laboratory of Genetics, Wageningen Institute of Animal Sciences, Wageningen, The Netherlands

    Peter de Boer

  5. Department of Cell Biology, School of Medicine, Valladolid University, Valladolid, Spain

    Josefa Blanco-Rodríguez

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  1. Shantha K. Mahadevaiah
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Correspondence to Paul S. Burgoyne.

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Mahadevaiah, S., Turner, J., Baudat, F. et al. Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27, 271–276 (2001). https://doi.org/10.1038/85830

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