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.

Nature Communications
|November 3, 2015
PubMed

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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