Despite recent advances in understanding the molecular mechanisms of DNA damage response and repair in oocytes, it remains unclear how oocytes deal with DNA damage during meiosis. Korean researchers at Sungkyunkwan University (SKKU) have shed on new light on this issue by uncovering the molecular mechanisms underlying DNA damage response and repair during oocyte meiosis. Their findings were published in the journal Nucleic Acids Research on March 31.

The researchers found that CIP2A complexes with p-MDC1 and p-TOPBP1 at the spindle poles during meiosis in oocytes, then moves along spindle microtubules and is recruited to chromosomes via kinetochores and centromeres in response to DNA damage. They also found that the relocation of the CIP2A–MDC1–TOPBP1 complex towards chromosomes ensures the recruitment of downstream repair factors such as BRCA1 and 53BP1, resulting in DNA repair during oocyte meiosis.

In light of these findings, Prof. Oh stated, “Our research has provided new insights into the DNA damage response and repair mechanisms during oocyte meiosis, which are critical for maintaining genome integrity and developing strategies to preserve female fertility”. “We are planning to continue investigating ways to control the DNA damage response and repair in mammalian oocytes to prevent the decline of oocyte quality associated with aging”, Prof. Oh said.

Schematic model of DNA damage response that occurs in oocytes during meiosis I.

[Reference] Leem, Jiyeon et al. “Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.” Nucleic acids research, gkad213. 31 Mar. 2023, doi:10.1093/nar/gkad213

[Main Author] Jiyeon Leem (Sungkyunkwan University), Jeong Su Oh (Sungkyunkwan University)

* Contact email : Professor Jeong Su Oh (ohjs@skku.edu)