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RAD51在猪卵母细胞体外成熟过程中维持染色体完整性和线粒体分布。

RAD51 maintains chromosome integrity and mitochondrial distribution during porcine oocyte maturation in vitro.

作者信息

Jin Zhe-Long, Kim Nam-Hyung

机构信息

Department of Animal Sciences, Chungbuk National University, Cheongju 361-763, Korea.

出版信息

J Reprod Dev. 2017 Oct 18;63(5):489-496. doi: 10.1262/jrd.2017-078. Epub 2017 Jul 30.

Abstract

DNA repair protein RAD51 homolog 1 (RAD51) plays a central role in homologous recombination (HR) repair of DNA breaks. HR depends on the formation of a RAD51 recombinase filament that facilitates strand invasion. However, the role of RAD51 during porcine oocyte maturation is unknown. The objective of this study was to investigate the expression and function of RAD51 during porcine oocyte maturation in vitro. RAD51 was mainly localized to the nucleus at the germinal vesicle (GV) stage, and was widely distributed in the cytoplasm between the GV breakdown (GVBD) and metaphase II stage. DNA damage induced by etoposide was accompanied by the formation of RAD51 foci that were colocalized with γH2AX. Inhibition of RAD51 increased DNA damage and induced metaphase I arrest along with spindle defects, chromosomal misalignment, and abnormal spindle assembly checkpoint (SAC) activity. Inhibition of RAD51 also increased ROS levels and led to an abnormal mitochondrial distribution. Our results indicate that RAD51 plays a critical role in maintaining chromosome integrity and mitochondrial activity during porcine oocyte maturation.

摘要

DNA修复蛋白RAD51同源物1(RAD51)在DNA断裂的同源重组(HR)修复中起核心作用。HR依赖于促进链入侵的RAD51重组酶细丝的形成。然而,RAD51在猪卵母细胞成熟过程中的作用尚不清楚。本研究的目的是调查RAD51在猪卵母细胞体外成熟过程中的表达和功能。RAD51在生发泡(GV)期主要定位于细胞核,在GV破裂(GVBD)和中期II期之间广泛分布于细胞质中。依托泊苷诱导的DNA损伤伴随着与γH2AX共定位的RAD51焦点的形成。抑制RAD51会增加DNA损伤,并导致中期I停滞,同时伴有纺锤体缺陷、染色体排列紊乱和异常的纺锤体组装检查点(SAC)活性。抑制RAD51还会增加活性氧水平,并导致线粒体分布异常。我们的结果表明,RAD51在猪卵母细胞成熟过程中对维持染色体完整性和线粒体活性起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf3/5649098/150d236f97be/jrd-63-489-g001.jpg

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