Expression of the Ku70 subunit (XRCC6) and protection from low dose ionizing radiation during zebrafish embryogenesis
Expression of the Ku70 subunit (XRCC6) and protection from low dose ionizing radiation during zebrafish embryogenesis
复制标题
DOI：
10.1016/j.neulet.2007.05.045
复制
发表时间：
2007-07-11
影响因子：
2.5
通讯作者：
Kozlowski, David J.
中科院分区：
文献类型：
--
作者：
Bladen, Catherine L.;Navarre, Sammy;Kozlowski, David J.
Ku 70蛋白是XRCC 6基因的产物，是DNA修复的非同源末端连接（NHEJ）途径的组成部分，可保护细胞免受辐射诱导的DNA损伤的影响。尽管Ku 70在脊椎动物胚胎发生过程中的空间表达尚未被描述，但DNA修复蛋白通常被认为是所有细胞中辐射防护所需的“管家”基因。在这里，我们报告的斑马鱼Ku 70同源基因的克隆和表征。原位杂交和RT-PCR分析表明，Ku 70 mRNA由母体提供，并在胚胎分裂球中均匀表达。后来在胚胎发育过程中，合子转录Ku 70 mRNA特异性地积累在神经组织中，包括视网膜和发育中大脑的增殖区域。在没有遗传毒性胁迫的情况下，rnorpholino介导的Ku 70表达的敲低不影响斑马鱼胚胎发生。然而，将注射了Ku 70吗啉的胚胎暴露于低剂量的电离辐射会导致整个发育中的大脑、脊髓和尾部的显著细胞死亡。这些结果表明，Ku 70蛋白在保护胚胎发育过程中的神经系统免受辐射诱导的DNA损伤中起着至关重要的作用。出版社：Elsevier爱尔兰Ltd.
The Ku70 protein, a product of the XRCC6 gene, is a component of the nonhomologous end-joining (NHEJ) pathway of DNA repair, which protects cells from the effects of radiation-induced DNA damage. Although the spatial expression of Ku70 during vertebrate embryogenesis has not been described, DNA repair proteins are generally considered to be '' housekeeping '' genes, which are required for radioprotection in all cells. Here, we report the cloning and characterization of the zebrafish Ku70 ortholog. In situ hybridization and RT-PCR analyses demonstrate that Ku70 mRNA is maternally provided and expressed uniformly among embryonic blastomeres. Later during embryogenesis, zygotically transcribed Ku70 mRNA specifically accumulates in neural tissue, including the retina and proliferative regions of the developing brain. In the absence of genotoxic stress, rnorpholino-mediated knockdown of Ku70 expression does not affect zebrafish embryogenesis. However, exposure of Ku70 morpholino-injected embryos to low doses of ionizing radiation leads to marked cell death throughout the developing brain, spinal cord, and tail. These results suggest that Ku70 protein plays a crucial role in protecting the developing nervous system from radiation-induced DNA damage during embryogenesis. Published by Elsevier Ireland Ltd.