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Cohesin SMC1β is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination

Nature Cell Biology volume 6, pages 555–562 (2004)Cite this article

Abstract

Sister chromatid cohesion ensures the faithful segregation of chromosomes in mitosis and in both meiotic divisions1,2,3,4. Meiosis-specific components of the cohesin complex, including the recently described SMC1 isoform SMC1β5, were suggested to be required for meiotic sister chromatid cohesion and DNA recombination. Here we show that SMC1β-deficient mice of both sexes are sterile. Male meiosis is blocked in pachytene; female meiosis is highly error-prone but continues until metaphase II. Prophase axial elements (AEs) are markedly shortened, chromatin extends further from the AEs, chromosome synapsis is incomplete, and sister chromatid cohesion in chromosome arms and at centromeres is lost prematurely. In addition, crossover-associated recombination foci are absent or reduced, and meiosis-specific perinuclear telomere arrangements are impaired. Thus, SMC1β has a key role in meiotic cohesion, the assembly of AEs, synapsis, recombination, and chromosome movements.

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Figure 1: Immunofluorescence labelling of spread spermatocytes.
Figure 2: Chromatin compaction and telomere arrangement.
Figure 3: Recombination-related proteins in Smc1β+/+ and Smc1β−/− spermatocytes.
Figure 4: Analysis of OA-treated spermatocytes.
Figure 5: Multiple defects of female meiosis in Smc1β−/− mice.

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Acknowledgements

We acknowledge the support of the Mount Sinai Mouse Genetics Shared Research Facility (K. Kelley), funded by a grant from the NIH/NCI (R24CA88302). We thank A. Pastink, J.-M. Peters, T. de Lange, P. de Boer, P. Cohen, P. Moens and T. Ashley for generous gifts of antibodies; A. Firooznia for the preparation of recombinant STAG3 antigen and anti-STAG3 antibody; and E. de Boer for the preparation of recombinant MLH1 antigen and anti-MLH1 antibody. This work was supported by a grant from the NIH (GM62517) to R.J., a grant from the DFG (Sche350/8-4) to H.S., a grant from the NIH (HD37502) to P.A.H., and a grant from the EU (contract no. QLK3-2000-00365) to C.H.

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Author notes

  1. Ekaterina Revenkova, Maureen Eijpe, Bodo Liebe and Harry Scherthan: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, 10029, NY, USA

    Ekaterina Revenkova & Rolf Jessberger

  2. Molecular Genetics Group, Wageningen University, Wageningen, 6703 BD, The Netherlands

    Maureen Eijpe & Christa Heyting

  3. Department of Genetics, Case Western Reserve University, Cleveland, 44106, OH, USA

    Craig A. Hodges & Patricia A. Hunt

  4. Max Planck Institute for Molecular Genetics, Berlin, D-14195, Germany

    Bodo Liebe & Harry Scherthan

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  1. Ekaterina Revenkova
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Correspondence to Rolf Jessberger.

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Revenkova, E., Eijpe, M., Heyting, C. et al. Cohesin SMC1β is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nat Cell Biol 6, 555–562 (2004). https://doi.org/10.1038/ncb1135

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