9.9
CiteScore
7.1
Impact Factor
Volume 51 Issue 12
Dec.  2024

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

doi: 10.1016/j.jgg.2024.09.005
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
  • 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.

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