DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation.
DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation.
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DOI：
10.1371/journal.pone.0053358
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sprung CN
中科院分区：
文献类型：
--
作者：
Forrester HB;Li J;Hovan D;Ivashkevich AN;Sprung CN
DNA 修复是维持基因组稳定性所需的重要细胞过程。在正常生理条件下，每个细胞每天都会遭受数千个 DNA 损伤。电离辐射 (IR) 是一种主要的 DNA 损伤剂，可由天然和人造来源产生。辐射暴露的一个常见来源是通过其在医学诊断或治疗中的使用，例如癌症放射治疗，患者接受相对较高的剂量。为了了解详细的 DNA 修复基因转录对高剂量 IR 的反应，进行了基因表达外显子阵列研究，并检查了两种不同细胞类型（淋巴母细胞系和原代成纤维细胞）对辐射的反应。这些外显子阵列可检测整个基因的表达水平，并具有高灵敏度和识别替代转录本的能力的优点。我们发现了一系列 DNA 修复基因，包括一些以前未报道过的基因，它们会根据辐射进行调节。对 DNA 修复转录的详细剂量和时间过程动力学进行了研究，并利用 PCR 方法验证了结果。在几个 DNA 修复基因中鉴定出了响应 IR 的替代转录产物，包括 RRM2B 和 XPC，其中发现了替代起始位点。这些研究增进了人们对 DNA 修复转录反应的认识。
DNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal physiological conditions. Ionizing radiation (IR) is a major DNA damaging agent that can be produced by both natural and man-made sources. A common source of radiation exposure is through its use in medical diagnostics or treatments such as for cancer radiotherapy where relatively high doses are received by patients. To understand the detailed DNA repair gene transcription response to high dose IR, gene expression exon array studies have been performed and the response to radiation in two divergent cell types, lymphoblastoid cell lines and primary fibroblasts, has been examined. These exon arrays detect expression levels across the entire gene, and have the advantage of high sensitivity and the ability to identify alternative transcripts. We found a selection of DNA repair genes, including some not previously reported, that are modulated in response to radiation. Detailed dose and time course kinetics of DNA repair transcription was conducted and results have been validated utilizing PCR methods. Alternative transcription products in response to IR were identified in several DNA repair genes including RRM2B and XPC where alternative initiation sites were found. These investigations have advanced the knowledge about the transcriptional response of DNA repair.
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DOI：
10.1056/nejmra0809889
发表时间：
2010-05-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
D'Andrea AD
通讯作者：
D'Andrea AD
影响因子：
64.5
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
通讯作者：
KOLODNER, R
影响因子：
5.6
作者：
Batty, D;Rapic'-Otrin, V;Wood, RD
通讯作者：
Wood, RD
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ
影响因子：
3.6
作者：
Amundson, SA;Patterson, A;Fornace, AJ
通讯作者：
Fornace, AJ