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Damage of telomeric DNA by active oxygen radicals

活性氧自由基对端粒 DNA 的损伤

基本信息

批准号：
17570092
负责人：
KANAORI Kenji
金额：
$ 2.18万
依托单位：
Kyoto Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570092/
关键词：
active oxygen telomere DNA lesion Electron spin resonance radical NMR

项目摘要

We have studied DNA damages of telomeric DNA by the active-oxygen. G-quartet structure which is the structure of the telomere deoxyribonucleic acid was reviewed in detail about a wide range of alkali metal ions, because the structural change occurred with the difference in the alkali metal ion and the radical-reaction between DNA and radicals was changed. Based on the structural information, the damages of the nucleic acid were observed in the direct measurement, and we have observed the time change. At present, those are being clarified by the mass analysis and NMR. In the direct measurement of the reaction between DNA and radicals, however, our previous systems could not be applied because of the low concentration and fast decay of the radicals. Therefore, we examined the mixer and pass of the stopped-flow instrument, and made the new system. Moreover, in the detecting means, we have improved capillary flow-cell and used it. It succeeded in incorporating an irradiation system into stopped-flow-ESR measurement system by the improvement and making active-oxygen radical species react to the occurrence and the biological-sample efficiently. It established a way of detecting nucleic acid radical. Also, some spin-trap reagents were obtained by the chemical synthesis formed them by the recrystallization. They made us selectively detect the radicals. Currently, we applied this system to the research of telomeric DNA damages by the active-oxygen of the amino acid. At present, the structure singularity of the radical-reaction of the telomere deoxyribonucleic acid is clarifying the mechanism of the damage of the deoxyribonucleic acid all together with the result of the clarifying and NMR.

研究了活性氧对端粒DNA的损伤作用。由于碱金属离子的不同会引起端粒DNA结构的变化，从而改变DNA与自由基的反应，因此对端粒DNA的G-四重结构进行了详细的综述。基于结构信息，在直接测量中观察到核酸的损伤，并且我们观察到了时间变化。目前，这些正在通过质量分析和NMR来澄清。然而，在DNA与自由基反应的直接测量中，由于自由基的浓度低且衰减快，我们以前的系统不能应用。为此，我们对停流器的混合器和通道进行了研究，并制作了新的系统。另外，在检测手段上，我们对毛细管流动池进行了改进和应用，通过改进，成功地将辐照系统与停流ESR测量系统相结合，使活性氧自由基物种有效地与生物样品发生反应。建立了一种检测核酸自由基的方法。此外，还通过化学合成方法获得了一些自旋陷阱试剂，这些试剂是通过重结晶形成的。他们让我们有选择地检测激进分子。目前，我们将该系统应用于氨基酸活性氧对端粒DNA损伤的研究。目前，端粒脱氧核糖核酸的自由基反应的结构奇异性正与核磁共振的结果一起阐明脱氧核糖核酸的损伤机制。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The roles of conserved amino acids on substrate binding and conformational integurity of C1pB N-terminal domain

保守氨基酸对 C1pB N 端结构域底物结合和构象完整性的作用

DOI：
发表时间：
2006
期刊：
Biochemistry 45
影响因子：
0
作者：
Tanaka;N.
通讯作者：
N.

Pyrene is highly emissive when attached to the RNA duplex but not to the DNA duplex: the structural basis of this difference.

DOI：
10.1093/nar/gki889
发表时间：
2005
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Nakamura M;Fukunaga Y;Sasa K;Ohtoshi Y;Kanaori K;Hayashi H;Nakano H;Yamana K
通讯作者：
Yamana K

Interaction of gymnemic acid with cyclodextrins analyzed by isothermal titration calorimetry, NMR and dynamic light scattering