Marangos, P;
Stevense, M;
Niaka, K;
Lagoudaki, M;
Nabti, I;
Jessberger, R;
Carroll, J;
(2015)
DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age.
Nature Communications
, 6
, Article 8706. 10.1038/ncomms9706.
Preview |
Text
DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age.pdf Download (1MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms9706 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms9706 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1474517 |
Archive Staff Only
 |
View Item |
