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DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age

Author

Listed:
  • Petros Marangos

    (UCL
    University of Ioannina)

  • Michelle Stevense

    (Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology)

  • Konstantina Niaka

    (University of Ioannina)

  • Michaela Lagoudaki

    (University of Ioannina)

  • Ibtissem Nabti

    (UCL)

  • Rolf Jessberger

    (Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology)

  • John Carroll

    (UCL
    Development and Stem Cells Program, Monash University)

Abstract

In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes from aged mice. These data lead us to propose that the SAC is a major gatekeeper preventing the progression of oocytes harbouring DNA damage. The SAC therefore acts to integrate protection against both aneuploidy and DNA damage by preventing production of abnormal mature oocytes and subsequent embryos. Finally, we suggest escaping this DNA damage checkpoint in maternal ageing may be one of the causes of increased chromosome anomalies in oocytes and embryos from older mothers.

Suggested Citation

  • Petros Marangos & Michelle Stevense & Konstantina Niaka & Michaela Lagoudaki & Ibtissem Nabti & Rolf Jessberger & John Carroll, 2015. "DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9706
    DOI: 10.1038/ncomms9706
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    Cited by:

    1. Fei Sun & Nourhan Nashat Ali & Daniela Londoño-Vásquez & Constantine A. Simintiras & Huanyu Qiao & M. Sofia Ortega & Yuksel Agca & Masashi Takahashi & Rocío M. Rivera & Andrew M. Kelleher & Peter Suto, 2024. "Increased DNA damage in full-grown oocytes is correlated with diminished autophagy activation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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