CtIP regulates G2/M transition and bipolar spindle assembly during mouse oocyte meiosis

Wei Yue; Hong-Yong Zhang; Heide Schatten; Tie-Gang Meng; Qing-Yuan Sun

doi:10.1016/j.jgg.2024.09.005

Volume 51 Issue 12

Dec. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(12): 1435-1446

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CtIP regulates G2/M transition and bipolar spindle assembly during mouse oocyte meiosis

doi: 10.1016/j.jgg.2024.09.005

a. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
b. Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, Guangdong 524045, China;
c. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA;
d. Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, China

Funds:

This study was supported by National Natural Science Foundation of China (32570854), Science and Technology Program of Guangzhou, China (2023A03J0258) and Guangdong Basic and Applied Basic Research Foundation, China (2023B1515120027).

Received Date: 2024-06-29
Accepted Date: 2024-09-05
Rev Recd Date: 2024-09-04

Available Online: 2025-06-05

Publish Date: 2024-09-12

Abstract

Abstract

CtBP-interacting protein (CtIP) is known for its multifaceted roles in DNA repair and genomic stability, directing the homologous recombination-mediated DNA double-stranded break repair pathway via DNA end resection, an essential error-free repair process vital for genome stability. Mammalian oocytes are highly prone to DNA damage accumulation due to prolonged G2/prophase arrest. Here, we explore the functions of CtIP in meiotic cell cycle regulation via a mouse oocyte model. Depletion of CtIP by siRNA injection results in delayed germinal vesicle breakdown and failed polar body extrusion. Mechanistically, CtIP deficiency increases DNA damage and decreases the expression and nuclear entry of CCNB1, resulting in marked impairment of meiotic resumption, which can be rescued by exogenous CCNB1 overexpression. Furthermore, depletion of CtIP disrupts microtubule-organizing centers coalescence at spindle poles as indicated by failed accumulation of γ-tubulin, p-Aurora kinase A, Kif2A, and TPX2, leading to abnormal spindle assembly and prometaphase arrest. These results provide valuable insights into the important roles of CtIP in the G2/M checkpoint and spindle assembly in mouse oocyte meiotic cell cycle regulation.
- CtIP,
- Meiosis,
- G2/M transition,
- Spindle assembly,
- Oocyte

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References(56)

References

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