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Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
DNA damage responses in mammalian oocytes
Josie K Collins1, Keith T Jones1
1Centre for Biological SciencesFaculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK k.t.jones@soton.ac.uk; jkc1g10@soton.ac.uk.
Abstract:
DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence, it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here, the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocytes helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such maturing oocytes are arrested at metaphase I due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and considered to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore, the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I uncovers a novel second function for this ubiquitous cellular checkpoint.
Insights
DNA damage during egg cell development can cause infertility. Oocytes utilize the Spindle Assembly Checkpoint to prevent damaged eggs, revealing a new role for this crucial cellular pathway.
Area of Science:
- Reproductive biology
- Cellular biology
- Genetics
Background:
- DNA damage during meiosis can lead to infertility and miscarriage.
- Oocytes must detect and respond to DNA damage to ensure healthy egg formation.
- Previous understanding suggested the Spindle Assembly Checkpoint is weak in oocytes.
Purpose of the Study:
- To review strategies oocytes use to respond to DNA damaging events.
- To highlight a novel pathway in oocytes preventing mature eggs with DNA damage.
- To explore the role of the Spindle Assembly Checkpoint in oocyte DNA damage response.
Main Methods:
- Review of recent evidence on oocyte DNA damage response pathways.
- Analysis of oocyte behavior following induced DNA damage.
- Investigation of Spindle Assembly Checkpoint activation in maturing oocytes.
Main Results:
- Fully grown oocytes with DNA damage do not arrest but resume meiosis and stall in the first meiotic division.
- The Spindle Assembly Checkpoint is actively involved in arresting maturing oocytes at metaphase I.
- This indicates a previously unrecognized function of the Spindle Assembly Checkpoint in oocyte DNA damage response.
Conclusions:
- Oocytes employ a novel mechanism involving the Spindle Assembly Checkpoint to prevent the formation of eggs with DNA damage.
- The Spindle Assembly Checkpoint has a second, critical function in oocyte DNA damage response during meiosis I.
- This finding has implications for understanding infertility and developing reproductive health strategies.
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