Common mitochondrial DNA mutations generated through DNA-mediated charge transport.
Common mitochondrial DNA mutations generated through DNA-mediated charge transport.
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DOI：
10.1021/bi801570j
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发表时间：
2009-02-03
期刊：
影响因子：
2.9
通讯作者：
Barton, Jacqueline K.
中科院分区：
文献类型：
--
作者：
Merino, Edward J.;Davis, Molly L.;Barton, Jacqueline K.
人类线粒体 DNA 中因铑光氧化剂氧化而产生的突变位点已被确定。 HeLa 细胞与[Rh(phi)2bpy]Cl3（phi = 9,10-菲醌二亚胺）（一种嵌入光氧化剂）一起孵育，以使复合物进入细胞并结合线粒体 DNA。 DNA 结合的 [Rh(phi)2bpy]3+ 的光激发可以通过 DNA 介导的电荷传输从远处促进鸟嘌呤的氧化。在与铑复合物一起孵育的细胞经过两轮光解和生长后，通过手动测序评估了部分线粒体基因组中的 DNA 突变。突变模式与重复鸟嘌呤束中 dG 到 dT 的颠换一致。值得注意的是，发现的突变模式与之前看到的氧化损伤热点重叠。这些突变发现于保守序列块 II 内，保守序列块 II 是参与 DNA 复制的关键调控元件，并且这些突变已被确定为氧化损伤集中的低氧化电位位点。基于这种突变分析及其与长程氧化损伤位点的对应关系，我们推断 DNA 电荷传输在产生这些突变中发挥着关键作用，从而在氧化应激下调节线粒体 DNA 复制中发挥着关键作用。
Mutation sites that arise in human mitochondrial DNA as a result of oxidation by a rhodium photooxidant have been identified. HeLa cells were incubated with [Rh(phi)2bpy]Cl3 (phi = 9,10-phenanthrenequinone diimine), an intercalating photooxidant, to allow the complex to enter the cell and bind mitochondrial DNA. Photoexcitation of DNA-bound [Rh(phi)2bpy]3+ can promote the oxidation of guanine from a distance through DNA-mediated charge transport. After two rounds of photolysis and growth of cells incubated with the rhodium complex, DNA mutations in a portion of the mitochondrial genome were assessed via manual sequencing. The mutational pattern is consistent with dG to dT transversions in the repetitive guanine tracts. Significantly, the mutational pattern found overlaps oxidative damage hot spots seen previously. These mutations are found within conserved sequence block II, a critical regulatory element involved in DNA replication, and these have been identified as sites of low oxidation potential to which oxidative damage is funneled. Based upon this mutational analysis and its correspondence to sites of long range oxidative damage, we infer a critical role for DNA charge transport in generating these mutations and, thus, in regulating mitochondrial DNA replication under oxidative stress.
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影响因子：
8.8
作者：
Slebos, R. J. C.;Li, M.;Vadivelu, S.;Burkey, B. B.;Netterville, J. L.;Sinard, R.;Gilbert, J.;Murphy, B.;Chung, C. H.;Shyr, Y;Yarbrough, W. G.
通讯作者：
Yarbrough, W. G.
影响因子：
15
作者：
Sugiyama, H;Saito, I
通讯作者：
Saito, I
DOI：
10.1073/pnas.96.15.8353
发表时间：
1999-07-20
影响因子：
11.1
作者：
Henderson, PT;Jones, D;Schuster, GB
通讯作者：
Schuster, GB
影响因子：
2.9
作者：
Merino, Edward J.;Barton, Jacqueline K.
通讯作者：
Barton, Jacqueline K.
影响因子：
4.8
作者：
Pham, Xuan Hoi;Farge, Geraldine;Falkenberg, Maria
通讯作者：
Falkenberg, Maria