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

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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 prophasearrested 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-arrested oocytes. However, we show that, when apoptosis is inhibited, severe DNA damage is corrected via homologous recombination repair. The repair is sufficient to support fertility and maintain health and genetic fidelity in offspring. Thus, despite the preferential induction of apoptosis following exogenously induced genotoxic stress, prophase-arrested oocytes are highly capable of functionally efficient DNA repair. These data implicate DNA repair as a key quality control mechanism in the female germ line and a critical determinant of fertility and genetic integrity.

Original languageEnglish
Pages (from-to)11513–11522
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number21
DOIs
Publication statusPublished - 26 May 2020

Keywords

  • DNA repair
  • oocytes
  • fertility
  • apoptosis
  • DNA damage

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