广东省第二人民医院孙青原课题组发现，CtIP在小鼠卵母细胞减数分裂过程中，调控G2/M转换及双极纺锤体组装。相关论文于2024年9月12日在线发表在《遗传学报》上。

研究人员表示，CtBP相互作用蛋白（CtIP）因其在DNA修复和基因组稳定性中的多重作用而闻名，尤其通过DNA末端切除引导同源重组介导的DNA双链断裂（DSB）修复路径，这是一种维持基因组稳定性的关键无误差修复过程。哺乳动物卵母细胞由于长期处于G2/前期停滞状态，极易积累DNA损伤。

研究人员通过小鼠卵母细胞模型，探讨了CtIP在减数分裂细胞周期调控中的功能。通过siRNA注射敲减CtIP，导致生发泡破裂延迟以及无法完成第一极体排出。机制上，CtIP缺失增加了DNA损伤，降低了CCNB1的表达和核进入，显著阻碍了减数分裂的恢复，而这种阻碍可以通过外源性CCNB1的过表达得以拯救。

此外，CtIP耗减破坏了纺锤体极处MTOC的聚合，表现为γ-微管蛋白、磷酸化Aurora激酶A、Kif2A和TPX2的积累失败，进而导致异常的纺锤体组装和前中期停滞。这些结果为CtIP在小鼠卵母细胞减数分裂细胞周期调控中的，G2/M检查点和纺锤体组装中的重要作用提供了有价值的见解。

附：英文原文

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

Author: Qing-Yuan Sun d

Issue&Volume: 2024/09/12

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 (DSBs) 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 MTOCs 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.

DOI: 10.1016/j.jgg.2024.09.005

Source: https://www.sciencedirect.com/science/article/abs/pii/S167385272400242X