Oocytes progress beyond prophase in the presence of DNA damage.

Current Biology : CB
Petros Marangos, John Carroll

Abstract

In the female germline, DNA damage has the potential to induce infertility and even to lead to genetic abnormalities that may be propagated to the resulting embryo [1, 2]. The protracted arrest in meiotic prophase makes oocytes particularly susceptible to the accumulation of environmental insults, including DNA damage. Despite this significant potential to harm reproductive capacity, surprisingly little is known about the DNA damage response in oocytes. We show that double-strand breaks in meiotically competent G2/prophase-arrested mouse oocytes do not prevent entry into M phase, unless levels of damage are severe. This lack of an efficient DNA damage checkpoint is because oocytes fail to effectively activate the master regulator of the DNA damage response pathway, ATM (ataxia telangiectasia mutated) kinase. In addition, instead of inhibiting cyclin B-CDK1 through destruction of Cdc25A phosphatase, oocytes utilize an inhibitory phosphorylation of Cdc25B. We conclude that oocytes are the only nontransformed cells that fail to launch a robust G2 phase DNA damage checkpoint and that this renders them sensitive to genomic instability.

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Citations

Apr 9, 2013·Molecular Aspects of Medicine·Anna Ajduk, Magdalena Zernicka-Goetz
Jan 31, 2014·Histochemistry and Cell Biology·T ZhangQ Y Sun
Dec 9, 2015·Molecular Reproduction and Development·HaiYang WangNam-Hyung Kim
Feb 14, 2016·Cell Cycle·Libor Macurek
Jan 9, 2016·Cell Cycle·Alexandra MayerPetr Solc
Dec 29, 2015·Cell Cycle·Libor Macurek
Oct 7, 2015·Journal of Assisted Reproduction and Genetics·P TulayS B SenGupta
Jan 20, 2015·Cell Biology International·Zi-Li Lin, Nam-Hyung Kim
Aug 5, 2015·Journal of Assisted Reproduction and Genetics·Giovanni CoticchioRubens Fadini
Dec 3, 2014·Fertility and Sterility·Franck PellestorGeneviève Lefort
Apr 14, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Josie Collins, Keith Thomas Jones
Nov 15, 2016·Scientific Reports·Mukhri HamdanSimon I R Lane
Mar 21, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Chun-Jie HuangLi-Jun Huo
Apr 4, 2017·The Journal of Reproduction and Development·Fei LinHai-Xiang Sun
Dec 13, 2018·Human Reproduction Update·Jacinta H MartinBrett Nixon
Oct 12, 2018·Reproduction, Fertility, and Development·Bingyue ZhangPeiqing Cong
Nov 3, 2015·Nature Communications·Josie K CollinsKeith T Jones
Feb 8, 2019·Journal of Medical Genetics·Alexander GheldofWillem Verpoest
Jun 28, 2018·Scientific Reports·Jacinta H MartinBrett Nixon
Aug 2, 2019·Journal of Pineal Research·Jiyeon LeemJeong Su Oh
Aug 2, 2017·The Journal of Reproduction and Development·Zhe-Long Jin, Nam-Hyung Kim
Apr 25, 2020·The Journal of Cell Biology·Goutham Narayanan SubramanianHayden Anthony Homer
Dec 16, 2017·Human Reproduction Update·Jessica GreaneyHayden Homer

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