CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes
Abstract Background During oocyte maturation, DNA double-strand breaks (DSBs) can decrease oocyte quality or cause mutations. How DSBs are repaired in dividing oocytes and which factors influence DSB repair are not well understood. Results By analyzing DSB repair pathways in oocytes at different sta...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s12915-025-02142-w |
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| author | Tian-Jin Xia Feng-Yun Xie Juan Chen Xiao-Guohui Zhang Sen Li Qing-Yuan Sun Qin Zhang Shen Yin Xiang-Hong Ou Jun-Yu Ma |
| author_facet | Tian-Jin Xia Feng-Yun Xie Juan Chen Xiao-Guohui Zhang Sen Li Qing-Yuan Sun Qin Zhang Shen Yin Xiang-Hong Ou Jun-Yu Ma |
| author_sort | Tian-Jin Xia |
| collection | DOAJ |
| description | Abstract Background During oocyte maturation, DNA double-strand breaks (DSBs) can decrease oocyte quality or cause mutations. How DSBs are repaired in dividing oocytes and which factors influence DSB repair are not well understood. Results By analyzing DSB repair pathways in oocytes at different stages, we found that break-induced replication (BIR) and RAD51-mediated homology-directed repair (HDR) were highly active in germinal vesicle breakdown (GVBD) oocytes but suppressed in metaphase II (MII) oocytes and the BIR in oocytes was promoted by CDK1 activity. By culturing oocytes in different media, we found that high-energy media, such as DMEM, decreased CDK1 protein levels and suppressed BIR or HDR in MII oocytes. In contrast, 53BP1-mediated nonhomologous end joining (NHEJ) repair was inhibited in germinal vesicle (GV) and GVBD oocytes but promoted in MII oocytes, and NHEJ was not affected by DMEM medium and CDK1 activity. In addition, in DSB MII oocytes, polymerase theta-mediated end joining (TMEJ) was found to be suppressed by CDK1 activity and promoted by high-energy media. Conclusions In summary, MII oocytes exhibit high heterogeneity in DSB repair, which is regulated by both metabolic factors and CDK1 activity. These results not only expand our understanding of oocyte DSB repair but also contribute to the modification of in vitro maturation medium for oocytes. |
| format | Article |
| id | doaj-art-0bff3b4b84714c5bb1bf27d2d7392748 |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | BMC Biology |
| spelling | doaj-art-0bff3b4b84714c5bb1bf27d2d73927482025-02-09T12:54:20ZengBMCBMC Biology1741-70072025-02-0123111510.1186/s12915-025-02142-wCDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytesTian-Jin Xia0Feng-Yun Xie1Juan Chen2Xiao-Guohui Zhang3Sen Li4Qing-Yuan Sun5Qin Zhang6Shen Yin7Xiang-Hong Ou8Jun-Yu Ma9Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityReproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityCollege of Life Sciences, Qingdao Agricultural UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityAbstract Background During oocyte maturation, DNA double-strand breaks (DSBs) can decrease oocyte quality or cause mutations. How DSBs are repaired in dividing oocytes and which factors influence DSB repair are not well understood. Results By analyzing DSB repair pathways in oocytes at different stages, we found that break-induced replication (BIR) and RAD51-mediated homology-directed repair (HDR) were highly active in germinal vesicle breakdown (GVBD) oocytes but suppressed in metaphase II (MII) oocytes and the BIR in oocytes was promoted by CDK1 activity. By culturing oocytes in different media, we found that high-energy media, such as DMEM, decreased CDK1 protein levels and suppressed BIR or HDR in MII oocytes. In contrast, 53BP1-mediated nonhomologous end joining (NHEJ) repair was inhibited in germinal vesicle (GV) and GVBD oocytes but promoted in MII oocytes, and NHEJ was not affected by DMEM medium and CDK1 activity. In addition, in DSB MII oocytes, polymerase theta-mediated end joining (TMEJ) was found to be suppressed by CDK1 activity and promoted by high-energy media. Conclusions In summary, MII oocytes exhibit high heterogeneity in DSB repair, which is regulated by both metabolic factors and CDK1 activity. These results not only expand our understanding of oocyte DSB repair but also contribute to the modification of in vitro maturation medium for oocytes.https://doi.org/10.1186/s12915-025-02142-wOocytesDouble-strand breaksRAD5153BP1Break-induced replicationTheta-mediated end joining |
| spellingShingle | Tian-Jin Xia Feng-Yun Xie Juan Chen Xiao-Guohui Zhang Sen Li Qing-Yuan Sun Qin Zhang Shen Yin Xiang-Hong Ou Jun-Yu Ma CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes BMC Biology Oocytes Double-strand breaks RAD51 53BP1 Break-induced replication Theta-mediated end joining |
| title | CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes |
| title_full | CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes |
| title_fullStr | CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes |
| title_full_unstemmed | CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes |
| title_short | CDK1 mediates the metabolic regulation of DNA double-strand break repair in metaphase II oocytes |
| title_sort | cdk1 mediates the metabolic regulation of dna double strand break repair in metaphase ii oocytes |
| topic | Oocytes Double-strand breaks RAD51 53BP1 Break-induced replication Theta-mediated end joining |
| url | https://doi.org/10.1186/s12915-025-02142-w |
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