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

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). T...

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Bibliographic Details
Published in:Nature communications 2015-11, Vol.6 (1), p.8706-8706, Article 8706
Main Authors: Marangos, Petros, Stevense, Michelle, Niaka, Konstantina, Lagoudaki, Michaela, Nabti, Ibtissem, Jessberger, Rolf, Carroll, John
Format: Article
Language:English
Subjects:
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631/80/641/2187
Age
Animals
Arrests
Chromosomes
Developmental biology
DNA Damage
Female
Humanities and Social Sciences
Infertility
M Phase Cell Cycle Checkpoints
Maternal Age
Meiosis
Metaphase
Mice
Mice, Inbred C57BL
multidisciplinary
Oocytes - cytology
Pregnancy
Science
Science (multidisciplinary)
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Summary: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. DNA damage in mammalian oocytes can lead to infertility and developmental disorders. Here Marangos et al. show that the spindle assembly checkpoint responds to DNA damage by arresting oocytes in metaphase I, and this checkpoint becomes compromised as mice age.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms9706