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SMC1β-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction

Nature Genetics volume 37, pages 1351–1355 (2005)Cite this article

Abstract

Mitotic chromosome segregation is facilitated by the cohesin complex, which maintains physical connections between sister chromatids until anaphase. Meiotic cell division is considerably more complex, as cohesion must be released sequentially to facilitate orderly segregation of chromosomes at both meiosis I and meiosis II. This necessitates meiosis-specific cohesin components; recent studies in rodents suggest that these influence chromosome behavior during both cell division and meiotic prophase1,2. To elucidate the role of the meiosis-specific cohesin SMC1β (encoded by Smc1l2) in oogenesis, we carried out meiotic studies of female SMC1β-deficient mice. Our results provide the first direct evidence that SMC1β acts as a chiasma binder in mammals, stabilizing sites of exchange until anaphase. Additionally, our observations support the hypothesis that deficient cohesion is an underlying cause of human age-related aneuploidy.

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Figure 1: Prophase cells from wild-type and SMC1β-deficient oocytes.
Figure 2: Loss of cohesion is evident at the time of chromosome condensation in oocytes from SMC1β-deficient females.
Figure 3: Meiotic chromosomes from SMC1β-deficient females show further skewing of chiasmata placement and loss of cohesion with age.

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Acknowledgements

We thank T. Ashley and S. Varmuza for supplying antibodies for these studies. This work was supported by grants from the US National Institutes of Health (P.A.H., T.J.H. and R.J.).

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Authors and Affiliations

  1. Department of Genetics, Case Western Reserve University, Cleveland, 44106, Ohio, USA

    Craig A Hodges

  2. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Ekaterina Revenkova & Rolf Jessberger

  3. Department of Physiological Chemistry, Dresden University of Technology, Germany

    Rolf Jessberger

  4. Center for Reproductive Biology and School of Molecular Biosciences, Washington State University, Pullman, 99164, Washington, USA

    Terry J Hassold & Patricia A Hunt

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  1. Craig A Hodges
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  2. Ekaterina Revenkova
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  4. Terry J Hassold
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  5. Patricia A Hunt
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Correspondence to Patricia A Hunt.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Scoring of recombination events (MLH1 foci and chiasmata) in wildtype and Smc1β−/− oocytes. (PDF 334 kb)

Supplementary Fig. 2

Example of methodology used to compare relative position of DNA sequences on the SC and on condensed chromosomes. (PDF 84 kb)

Supplementary Fig. 3

Quantitative RT-PCR of Smc1β RNA in different aged wildtype oocytes. (PDF 155 kb)

Supplementary Table 1

Placement of MLH1 foci and chiasmata with respect to BAC probes on the X chromosome. (PDF 13 kb)

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Hodges, C., Revenkova, E., Jessberger, R. et al. SMC1β-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction. Nat Genet 37, 1351–1355 (2005). https://doi.org/10.1038/ng1672

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