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Updated: Mar 27, 2026
Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
DNA damage response during mouse oocyte maturation
Alexandra Mayer1, Vladimir Baran1,2, Yogo Sakakibara3
1a Institute of Animal Physiology and Genetics AS CR , Libechov , Czech Republic.
Abstract:
Because low levels of DNA double strand breaks (DSBs) appear not to activate the ATM-mediated prophase I checkpoint in full-grown oocytes, there may exist mechanisms to protect chromosome integrity during meiotic maturation. Using live imaging we demonstrate that low levels of DSBs induced by the radiomimetic drug Neocarzinostatin (NCS) increase the incidence of chromosome fragments and lagging chromosomes but do not lead to APC/C activation and anaphase onset delay. The number of DSBs, represented by γH2AX foci, significantly decreases between prophase I and metaphase II in both control and NCS-treated oocytes. Transient treatment with NCS increases >2-fold the number of DSBs in prophase I oocytes, but less than 30% of these oocytes enter anaphase with segregation errors. MRE11, but not ATM, is essential to detect DSBs in prophase I and is involved in H2AX phosphorylation during metaphase I. Inhibiting MRE11 by mirin during meiotic maturation results in anaphase bridges and also increases the number of γH2AX foci in metaphase II. Compromised DNA integrity in mirin-treated oocytes indicates a role for MRE11 in chromosome integrity during meiotic maturation.
Insights
Meiotic maturation in oocytes relies on MRE11, not ATM, to maintain DNA double-strand break (DSB) repair and chromosome integrity. This ensures proper chromosome segregation, preventing errors during meiosis.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Low levels of DNA double-strand breaks (DSBs) may not fully activate the ATM-mediated prophase I checkpoint in oocytes.
- Mechanisms protecting chromosome integrity during meiotic maturation require further investigation.
Purpose of the Study:
- To investigate the role of DNA double-strand breaks (DSBs) and associated proteins in maintaining chromosome integrity during oocyte meiotic maturation.
- To determine the involvement of MRE11 and ATM in DSB detection and repair during oocyte meiosis.
Main Methods:
- Live imaging of oocytes treated with Neocarzinostatin (NCS) to induce DSBs.
- Quantification of DSBs using γH2AX foci.
- Inhibition of MRE11 using mirin to assess its role in chromosome integrity.
Main Results:
- Neocarzinostatin (NCS) treatment increased DSBs but did not consistently activate the APC/C or delay anaphase onset.
- MRE11, not ATM, was essential for DSB detection in prophase I and H2AX phosphorylation in metaphase I.
- Inhibiting MRE11 led to anaphase bridges and increased DSBs in metaphase II oocytes, indicating compromised DNA integrity.
Conclusions:
- MRE11 plays a critical role in detecting DSBs and maintaining chromosome integrity during oocyte meiotic maturation.
- ATM is not essential for DSB detection in prophase I oocytes.
- Proper DNA repair mechanisms involving MRE11 are crucial for preventing segregation errors during oocyte meiosis.
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