Identification of potential radiation-responsive biomarkers based on human orthologous genes with possible roles in DNA repair pathways by comparison between Arabidopsis thaliana and homo sapiens.
Identification of potential radiation-responsive biomarkers based on human orthologous genes with possible roles in DNA repair pathways by comparison between Arabidopsis thaliana and homo sapiens.
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DOI：
10.1016/j.scitotenv.2019.135076
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Lei Zhao;Xinye He;Yuxuan Shang;Chengyu Bao;Ailin Peng;Xiaohua Lei;Pei Han;D. Mi;Yeqing Sun
中科院分区：
文献类型：
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作者：
Lei Zhao;Xinye He;Yuxuan Shang;Chengyu Bao;Ailin Peng;Xiaohua Lei;Pei Han;D. Mi;Yeqing Sun
随着核事故应急医学评价和治疗的迫切需要，快速可靠的电离辐射（IR）暴露量估算变得越来越重要。人类DNA修复基因可以作为评估IR暴露的重要候选生物标志物，但如何在DNA修复网络中找到足够敏感和特异的生物标志物仍然是一个挑战，尚未完全确定。DNA修复途径的保守特征可以促进跨学科研究，跨越动物和植物生物学之间的传统界限，目的是确定潜在的辐射响应生物标志物的未发现的人类DNA修复基因。本工作采用计算机同源比较的方法鉴定了A. thalianaDNA修复基因的研究，从而探索敏感、特异的人体辐射响应基因，以评价IR照射水平。结果表明，共有16个候选基因参与了同源重组（HR）和非同源末端连接（NHEJ）的DNA修复途径，其中大部分已被实验证实。此外，我们分析了这16个候选基因的基因表达模式，在几个人类转录微阵列数据集与不同的IR处理。结果表明，这些候选基因的基因表达水平在不同的辐射处理下发生了显着变化。基于这些结果，我们将这些推测的人类DNA修复基因整合到DNA修复途径中，为HR和NHEJ途径提供新的见解，这也可以为开发辐射生物标志物提供潜在的靶点。值得注意的是，两个推定的DNA修复基因，命名为ERCC1和ESCO 2，被认为是敏感和特异性的生物标志物，在响应γ射线照射。
Rapid and reliable ionization radiation (IR) exposure estimation has become increasingly important in environment due to the urgent requirement of medical evaluation and treatment in the event of nuclear accident emergency. Human DNA repair genes can be identified as important candidate biomarkers to assess IR exposure, while how to find the enough sensitive and specific biomarkers in the DNA repair networks is still challenged and not fully determined. The conserved features of DNA repair pathways may facilitate interdisciplinary studies that cross the traditional boundaries between animal and plant biology, with the aim of identifying undiscovered human DNA repair genes for potential radiation-responsive biomarkers. In this work, anin silicomethod of homologous comparison was performed to identify the human orthologues ofA. thalianaDNA repair genes, and thereby to explore the sensitive and specific human radiation-responsive genes to evaluate the IR exposure levels. The results showed that a total of 16 putative candidate genes were involved in the human DNA repair pathways of homologous recombination (HR) and non-homologous end joining (NHEJ), and most of them were confirmed by previous experiments. Additionally, we analyzed the gene expression patterns of these 16 candidate genes in several human transcript microarray datasets with different IR treatments. The results indicated that most of the gene expression levels for these candidate genes were significantly changed under different radiation treatments. Based on these results, we integrated these putative human DNA repair genes into the DNA repair pathways to propose new insights of the HR and NHEJ pathways, which can also provide the potential targets for the development of radiation biomarkers. Notably, two putative DNA repair genes, named ERCC1 and ESCO2, were identified and were considered to be the sensitive and specific biomarkers in response to γ-ray exposures.