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

Petros Marangos (), Michelle Stevense, Konstantina Niaka, Michaela Lagoudaki, Ibtissem Nabti, Rolf Jessberger and John Carroll
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Petros Marangos: UCL
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

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9706

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