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Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1

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Abstract

Disjunction of pairs of homologous chromosomes during the first meiotic division (MI) requires anaphase-promoting complex (APC)-mediated activation of separase in budding yeast1,2 and Caenorhabditis elegans3,4,5, but not Xenopus laevis6,7. It is not clear which model best fits the mammalian system. Here we show that homologue disjunction in mouse oocytes is dependent on proteolysis of the separase inhibitor securin and the Cdk1 regulatory sub-unit cyclin B1. Proteolysis of both proteins was entirely dependent on their conserved destruction box (D-box) motifs, through which they are targeted to the APC8. These data indicate that the mechanisms regulating homologue disjunction in mammalian oocytes are similar to those of budding yeast and C.elegans.

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Figure 1: Proteolysis of securin is required for homologue disjunction.

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Acknowledgements

We thank M. Sinclair and K Wilson for technical assistance, J. Pintor-Toro for human securin cDNA, J. Pines for human cyclin B1 cDNA, and J. Lukas for securin monoclonal antibody. This work was supported by a grant from Newcastle University Hospitals Special Trustees. H.H. is supported by a WellBeing Research Training Fellowship. The Wellcome Trust supported work in the McDougall lab.

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Author notes

  1. Alex McDougall

    Present address: UMR 7009 CNRS, Université Pierre et Marie Curie (Paris VI), Observetoire Océanologique, 06230, Villefranche-sur-Mer, France

Authors and Affiliations

  1. Cell and Developmental Physiology Research Group, School of Surgical and Reproductive Sciences, Bioscience Centre, International Centre for Life, Times Square, Newcastle upon Tyne, NE1 4EP, UK

    Mary Herbert & Hayden Homer

  2. Cell and Developmental Physiology Research Group, School of Cell and Molecular Bioscience, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

    Mark Levasseur & Alex McDougall

  3. Newcastle Fertility Centre, Bioscience Centre, International Centre for Life, Times Square, Newcastle upon Tyne, NE1 4EP, UK

    Katie Yallop & Alison Murdoch

Authors
  1. Mary Herbert
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  2. Mark Levasseur
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  3. Hayden Homer
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  4. Katie Yallop
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  5. Alison Murdoch
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  6. Alex McDougall
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Corresponding authors

Correspondence to Mary Herbert or Alex McDougall.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information, Fig. S1

Supplementary Information, Fig. S2 (DOC 177 kb)

Supplementary Methods (PDF 44 kb)

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Herbert, M., Levasseur, M., Homer, H. et al. Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1. Nat Cell Biol 5, 1023–1025 (2003). https://doi.org/10.1038/ncb1062

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  • DOI: https://doi.org/10.1038/ncb1062

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