Kim Kyeoung-Hwa, Park Ji-Hoon, Kim Eun-Young, Ko Jung-Jae, Park Kyung-Soon, Lee Kyung-Ah
Institute of Reproductive Medicine, Department of Biomedical Science, College of Life Science, CHA University, Pangyo-Ro 335, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Korea.
Sci Rep. 2016 Sep 28;6:34110. doi: 10.1038/srep34110.
Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I. Rad51-depleted oocytes showed chromosome misalignment and failures in spindle aggregation, affecting the completion of cytokinesis. We found that Rad51 depletion was accompanied by decreased ATP production and mitochondrial membrane potential and increased DNA degradation. We further demonstrated that the mitochondrial defect activated autophagy in Rad51-depleted oocytes. Taken together, we concluded that Rad51 functions to safeguard mitochondrial integrity during the meiotic maturation of oocytes.
Rad51是一种保守的真核生物蛋白，介导有丝分裂和减数分裂过程中发生的DNA双链断裂的同源重组修复。此外，当复制应激增加时，Rad51促进线粒体DNA合成。Rad51还通过维持胚胎干细胞中的G2/M转换来调节细胞周期进程。在本研究中，我们报道了Rad51在小鼠卵母细胞体外成熟过程中调节线粒体活性的新功能。通过向生发泡期卵母细胞注射Rad51双链RNA来抑制Rad51，导致减数分裂停滞在中期I。Rad51缺失的卵母细胞表现出染色体排列紊乱和纺锤体聚集失败，影响胞质分裂的完成。我们发现，Rad51缺失伴随着ATP产生减少、线粒体膜电位降低和DNA降解增加。我们进一步证明，线粒体缺陷激活了Rad51缺失的卵母细胞中的自噬。综上所述，我们得出结论，Rad51在卵母细胞减数分裂成熟过程中发挥作用以保护线粒体完整性。
