Analysis of a novel back-up repair system for UV-induced DNA damage in human cells.

分析一种新型后备修复系统，用于修复人体细胞中紫外线引起的 DNA 损伤。

基本信息

批准号：
15310036
负责人：
MATSUNAGA Tsukasa
金额：
$ 7.55万
依托单位：
Kanazawa University, Graduate School of Natural Science and Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We have established a super-sensitive detection method for measuring cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs) induced by biological doses of ultraviolet (UV) light and suggested that human cells might have a novel repair system mainly for 6-4PPs other than nucleotide excision repair which has been thought to be only repair system for those lesions in humans so far. In this study, we have obtained the following findings.1.The removal of 6-4PPs was observed even in the embryonic fibroblasts derived from xpa(-/-) or xpg(-/-) knock-out mice (30-50% after 24 hr). In addition, the removal of CPDs was also detected in those cells with a less efficiency (20-30% after 48 hr).2.HeLa cells stably expressing AlwNI-type mutant XPA did not show any impairment of nucleotide excision repair activity, suggesting that this mutant XPA protein does not have a dominant-negative effect.3.We have further sensitized the detection method for CPDs, enabling us to determine the repair kinetics of CPDs in cells exposed to non-killing doses of Was low as 0.1 J/m^2. Under this condition, we have found that xeroderma pimentosum cells significantly remove CPDs (〜40% after 48hr).4.We could observe some weak enhancement of repair efficiency after UV irradiation of 1 J/m^2 when the human cells had been pie-exposed to 0.2 J/m^2. However, we need more extensive experiments to conclude whether the back-up repair system is under the control of adaptive responses.Taken together with those results, we concluded that mammalian cells have a certain back-up repair system, independent of XPA and XPG, which removes mainly 6-4PP but also CPDs with a less efficiency.

我们已经建立了一种测量环丁烷嘧啶二聚体（CPD）和（6-4）光产物（6-4pp）的超敏感检测方法，生物剂量的紫外线（UV）光线（UV）光线，并建议人类可能对6--4PP的修复系统进行了新的修复系统，该系统仅是其他系统，而该系统可能是对这些系统的新型修复，而这些修复系统仅是这些系统，而该系统是该系统的范围。在这项研究中，我们获得了以下发现。1。即使在源自XPA（ - / - ）或XPG（ - / - ）敲除小鼠（24小时后30-50％）的胚胎成纤维细胞中观察到6-4pps的去除。此外，在那些具有效率较低的细胞中还检测到了CPD的去除（48小时后20-30％）。2.Hela细胞稳定表达alwni-type突变体XPA XPA XPA稳定的核丁基惊喜维修活动没有任何损害显示出对这种XPA蛋白的影响，表明该启用均具有较高的效率。暴露于非杀伤剂量的细胞中CPD的动力学低至0.1 j/m^2。在这种情况下，我们发现静脉皮肤菌细胞显着去除CPD（48小时后约40％）。4。当紫外线辐照1 J/m^2后，当人类细胞暴露于0.2 J/m^2时，我们可以观察到修复效率的提高较弱。但是，我们需要更广泛的实验，以包含备用修复系统是否在适应性响应的控制之下。与这些结果一起，我们得出结论，哺乳动物细胞具有一定的备份修复系统，与XPA和XPG无关，这主要消除了6-4pp，但也较低的CPD和效率较低。