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Updated: Mar 30, 2026

Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint
Josie K Collins1, Simon I R Lane1, Julie A Merriman1
1Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Abstract:
Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule-kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis.
Insights
Maternal DNA damage during meiosis activates the spindle assembly checkpoint (SAC) in oocytes, preventing embryo formation. This discovery reveals a crucial role for the SAC in detecting DNA damage, safeguarding female meiosis.
Area of Science:
- Reproductive biology
- Cellular biology
- Genetics
Background:
- Maternal DNA damage during meiosis is linked to infertility, birth defects, and abortions.
- The mechanism by which oocytes prevent the creation of DNA-damaged embryos remains unclear.
Purpose of the Study:
- To investigate whether fully grown oocytes possess a mechanism to prevent the formation of DNA-damaged embryos.
- To elucidate the role of the spindle assembly checkpoint (SAC) in response to DNA damage in oocytes.
Main Methods:
- Chemically induced double-strand breaks
- Ultraviolet B (UVB) radiation
- Ionizing radiation
Main Results:
- DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in oocytes.
- DNA damage effectively blocks anaphase-promoting complex activity, preventing mature egg formation.
- Unlike somatic cells, DNA damage does not impede mitotic progression in oocytes.
Conclusions:
- The meiotic spindle assembly checkpoint (SAC) has a critical, previously unrecognized role in detecting DNA damage in mammalian oocytes.
- This finding redefines the biological purpose of the meiotic SAC beyond its known function in error detection of microtubule-kinetochore interactions.
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