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双链DNA中的远程氧化损伤:G-C序列中凸起的G以及串联G/A错配的影响。

Long-range oxidative damage in duplex DNA: the effect of bulged G in a G-C tract and tandem G/A mispairs.

作者信息

Boone Edna, Schuster Gary B

机构信息

School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA.

出版信息

Nucleic Acids Res. 2002 Feb 1;30(3):830-7. doi: 10.1093/nar/30.3.830.

Abstract

Two series of duplex DNA oligomers were prepared having an anthraquinone derivative (AQ) covalently linked at a 5'-terminus. Irradiation of the AQ at 350 nm leads to injection of an electron hole (radical cation) into the DNA. The radical cation migrates through the DNA causing reaction primarily at G(n) sequences. In one series, GA tandem mispairs are inserted between GG steps to assess the effect of the mispair on the transport of the radical cation, reaction (damage) caused by the radical cation at the mispair, and repair of the resulting damage by formamidopyrimidine DNA glycosylase (Fpg). In the second series, a bulged guanine in a G3C2 sequence is interposed between the GG steps. These experiments reveal that neither G/A tandem mispairs nor bulged guanines are significant barriers to long-range charge migration in DNA. The radical cation does not cause reaction at guanines in the G/A tandem mispair. Reaction does occur at the bulged guanine, but it is repaired by Fpg.

摘要

制备了两系列双链DNA寡聚物,其5'-末端共价连接有蒽醌衍生物(AQ)。在350nm处照射AQ会导致向DNA中注入一个电子空穴(自由基阳离子)。自由基阳离子在DNA中迁移,主要在G(n)序列处引发反应。在一个系列中,GA串联错配插入在GG步之间,以评估错配对自由基阳离子传输、错配处自由基阳离子引起的反应(损伤)以及甲酰胺嘧啶DNA糖基化酶(Fpg)对由此产生的损伤的修复的影响。在第二个系列中,G3C2序列中的一个凸起的鸟嘌呤插入在GG步之间。这些实验表明,G/A串联错配和凸起的鸟嘌呤都不是DNA中长程电荷迁移的显著障碍。自由基阳离子不会在G/A串联错配中的鸟嘌呤处引发反应。凸起的鸟嘌呤处确实会发生反应,但会被Fpg修复。

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