Journal article

Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health

Jessica M Stringer, Amy Winship, Nadeen Zerafa, Matthew Wakefield, Karla Hutt

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2020

Abstract

Female fertility and offspring health are critically dependent on an adequate supply of high-quality oocytes, the majority of which are maintained in the ovaries in a unique state of meiotic prophase arrest. While mechanisms of DNA repair during meiotic recombination are well characterized, the same is not true for prophase-arrested oocytes. Here we show that prophase-arrested oocytes rapidly respond to γ-irradiation–induced DNA double-strand breaks by activating Ataxia Telangiectasia Mutated, phosphorylating histone H2AX, and localizing RAD51 to the sites of DNA damage. Despite mobilizing the DNA repair response, even very low levels of DNA damage result in the apoptosis of prophase-arreste..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

We thank from Monash Micro Imaging and the Monash Histology Platform for services and support. This work was supported by the National Health and Medical Research Council Grants 1050130 and 1100219 (to K.H.) and made possible through the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.