Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China; E-mail:
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming Yunnan, 650204, China.
Zool Res. 2018 Nov 18;39(6):387-395. doi: 10.24272/j.issn.2095-8137.2018.067. Epub 2018 Jun 15.
DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase(RAD51)focal accumulation at DNA DSBs. null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.
卵母细胞中的 DNA 损伤可导致不孕和出生缺陷。DNA 双链断裂（DSB）具有高度的危害性，会严重损害基因组的完整性。同源重组（HR）介导的 DNA DSB 修复在保护卵母细胞数量和质量方面发挥着主导作用。然而，关于卵母细胞中 HR 修复途径的关键因子知之甚少。在这里，我们鉴定了卵母细胞特异性基因作为小鼠卵母细胞中 HR 修复途径的一个新的关键组成部分。OOEP 对于 ATM 激酶的有效激活和 RAD51 重组酶（RAD51）在 DNA DSB 处的焦点积累是必需的。在体外 DNA 损伤刺激下，OOEP 缺失的卵母细胞在 DNA DSB 修复方面存在缺陷，并且易于发生细胞凋亡。此外，OOEP 缺失的卵母细胞表现出减数分裂成熟的延迟。因此，OOEP 通过维持基因组稳定性来维持卵母细胞数量和质量。随着母体年龄的增长，OOEP 的表达减少，提示其参与了母体衰老。
