Human Rad17 is phosphorylated upon DNA damage and also overexpressed in primary non-small cell lung cancer tissues.
Human Rad17 is phosphorylated upon DNA damage and also overexpressed in primary non-small cell lung cancer tissues.
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DOI：
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
X. Wang;L. Wang;M. Callister;J. Putnam;L. Mao;L. Li
中科院分区：
文献类型：
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作者：
X. Wang;L. Wang;M. Callister;J. Putnam;L. Mao;L. Li
spRAD 17基因是裂殖酵母裂殖酵母中DNA损伤和复制检查点的重要组成部分。spRAD 17的人类同源物hRAD 17的克隆表明，它表现出与复制辅助蛋白家族的结构相似性，该家族包括复制因子C复合物的亚基。我们分析了hRad17在DNA损伤剂作用下的磷酸化状态。我们的研究结果表明，hRad17的磷酸化发生后立即紫外线和电离辐射处理，并在约3小时达到峰值水平，这表明hRad17可能是一个组成部分的DNA损伤检查点。当分析原发性肿瘤样品时，我们观察到与匹配的正常组织对照相比，大多数（74%）非小细胞肺癌样品表现出显著更高水平的hRad17表达。相比之下，一组原发性结肠癌样品中的hRad17蛋白水平与正常结肠组织相比没有显示出升高的表达水平。这一观察结果表明，hRAD 17基因的功能可能参与肺癌的发展，并可能作为一个潜在的肿瘤标志物。
The spRAD17 gene is an essential component of the DNA damage and replication checkpoints in the fission yeast Schizosaccharomyces pombe. Cloning of the human homologue of spRAD17, hRAD17, indicated that it exhibits structural similarity with the replication accessory protein family, which include subunits of the Replication factor C complex. We have analyzed the phosphorylation status of hRad17 in response to DNA damaging agents. Our results showed that phosphorylation of hRad17 occurred immediately after UV and ionizing radiation treatment and reached peak level at approximately 3 h, suggesting that hRad17 may be a component of the DNA damage checkpoint. When primary tumor samples were analyzed, we observed that the majority (74%) of non-small cell lung carcinoma samples exhibited a significantly higher level of hRad17 expression compared with matched normal tissue controls. In contrast, hRad17 protein levels in a panel of primary colon carcinoma samples did not show an elevated level of expression compared with normal colon tissues. This observation suggests that the function of the hRAD17 gene may be involved in lung cancer development and may serve as a potential tumor marker.