- Title
- Double strand break DNA repair occurs via non-homologous end-joining in mouse MII oocytes
- Creator
- Martin, Jacinta H.; Bromfield, Elizabeth G.; Aitken, R. John; Lord, Tessa; Nixon, Brett
- Relation
- Scientific Reports Vol. 8, no. 9685, p. 9685-9685
- Publisher Link
- http://dx.doi.org/10.1038/s41598-018-27892-2
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2018
- Description
- The unique biology of the oocyte means that accepted paradigms for DNA repair and protection are not of direct relevance to the female gamete. Instead, preservation of the integrity of the maternal genome depends on endogenous protein stores and/or mRNA transcripts accumulated during oogenesis. The aim of this study was to determine whether mature (MII) oocytes have the capacity to detect DNA damage and subsequently mount effective repair. For this purpose, DNA double strand breaks (DSB) were elicited using the topoisomerase II inhibitor, etoposide (ETP). ETP challenge led to a rapid and significant increase in DSB (P=0.0002) and the consequential incidence of metaphase plate abnormalities (P=0.0031). Despite this, ETP-treated MII oocytes retained their ability to participate in in vitro fertilisation, though displayed reduced developmental competence beyond the 2-cell stage (P=0.02). To account for these findings, we analysed the efficacy of DSB resolution, revealing a significant reduction in DSB lesions 4 h post-ETP treatment. Notably, this response was completely abrogated by pharmacological inhibition of key elements (DNA-PKcs and DNA ligase IV) of the canonical non-homologous end joining DNA repair pathway, thus providing the first evidence implicating this reparative cascade in the protection of the maternal genome.
- Subject
- oocyte; DNA repair; female gametes; maternal genome; mRNA transcripts; oogenesis
- Identifier
- http://hdl.handle.net/1959.13/1389281
- Identifier
- uon:32871
- Identifier
- ISSN:2045-2322
- Rights
- © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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