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Maternal age-dependent APC/C-mediated decrease in securin causes premature sister chromatid separation in meiosis II

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  • Ibtissem Nabti

    (Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University
    University College London
    New York University Abu Dhabi)

  • Rosanna Grimes

    (University College London)

  • Hema Sarna

    (University College London)

  • Petros Marangos

    (University College London
    University of Ioannina
    Institute of Molecular Biology and Biotechnology-Foundation for Research and Technology)

  • John Carroll

    (Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University
    University College London)

Abstract

Sister chromatid attachment during meiosis II (MII) is maintained by securin-mediated inhibition of separase. In maternal ageing, oocytes show increased inter-sister kinetochore distance and premature sister chromatid separation (PSCS), suggesting aberrant separase activity. Here, we find that MII oocytes from aged mice have less securin than oocytes from young mice and that this reduction is mediated by increased destruction by the anaphase promoting complex/cyclosome (APC/C) during meiosis I (MI) exit. Inhibition of the spindle assembly checkpoint (SAC) kinase, Mps1, during MI exit in young oocytes replicates this phenotype. Further, over-expression of securin or Mps1 protects against the age-related increase in inter-sister kinetochore distance and PSCS. These findings show that maternal ageing compromises the oocyte SAC–APC/C axis leading to a decrease in securin that ultimately causes sister chromatid cohesion loss. Manipulating this axis and/or increasing securin may provide novel therapeutic approaches to alleviating the risk of oocyte aneuploidy in maternal ageing.

Suggested Citation

  • Ibtissem Nabti & Rosanna Grimes & Hema Sarna & Petros Marangos & John Carroll, 2017. "Maternal age-dependent APC/C-mediated decrease in securin causes premature sister chromatid separation in meiosis II," Nature Communications, Nature, vol. 8(1), pages 1-9, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15346
    DOI: 10.1038/ncomms15346
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    Cited by:

    1. Cheng-Jie Zhou & Xing-Yue Wang & Yan-Hua Dong & Dong-Hui Wang & Zhe Han & Xiao-Jie Zhang & Qing-Yuan Sun & John Carroll & Cheng-Guang Liang, 2022. "CENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Yun-Wen Wu & Sen Li & Wei Zheng & Yan-Chu Li & Lu Chen & Yong Zhou & Zuo-Qi Deng & Ge Lin & Heng-Yu Fan & Qian-Qian Sha, 2022. "Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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