Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence
Structural and dynamic effects of single 7-hydro-8-oxoguanine bases located in a frameshift target DNA sequence
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DOI：
10.1016/j.bpc.2005.06.003
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发表时间：
2005-10-22
影响因子：
3.8
通讯作者：
Mazzei, F
中科院分区：
文献类型：
--
作者：
Barone, F;Lankas, F;Mazzei, F
DNA 7-氢-8-氧代鸟嘌呤（8-oxoG）参与错配修复（MMR）缺陷细胞中HPRT基因G（6）序列的移码形成。使用基于该移码热点的寡核苷酸，我们研究了单个8-oxoG如何修饰G（6）区的结构和动力学性质。一个30纳秒的分子动力学（MD）模拟表明在紧邻病变的小沟的压缩。荧光偏振各向异性（FPA）和MD表明，8-oxoG增加DNA的扭转刚度，也限制了模型DNA复制模板/引物的单/双链DNA连接处的单链区域的移动。这些限制影响了Klenow（exo（-））DNA聚合酶的引物延伸效率。(c)2005 Elsevier B. V.保留所有权利。
DNA 7-hydro-8-oxoguanine (8-oxoG) is implicated in frameshift formation in an G(6) sequence of the HPRT gene in mismatch repair (MMR) defective cells. Using oligonucleotides based on this frameshift hotspot, we investigated how a single 8-oxoG modified the structural and dynamic properties of the G(6) tract. A 30 ns molecular dynamics (MD) simulation indicated compression of the minor groove in the immediate vicinity of the lesion. Fluorescence polarization anisotropy (FPA) and MD demonstrated that 8-oxoG increases DNA torsional rigidity and also constrains the movement of the single-stranded region at the single/double stranded DNA junction of model DNA replication template/primer. These constraints influenced the efficiency of primer extension by Klenow (exo(-)) DNA polymerase. (c) 2005 Elsevier B.V. All rights reserved.