Long-range oxidative damage in DNA/RNA duplexes.
Long-range oxidative damage in DNA/RNA duplexes.
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DNA/RNA 双链体中的长程氧化损伤。
DOI：
10.1021/bi0102961
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发表时间：
2001
期刊：
影响因子：
2.9
通讯作者：
Barton,JK
中科院分区：
文献类型：
--
作者：
Odom,DT;Barton,JK
DNA介导的长程电荷传输导致的氧化损伤在双链体DNA中容易且高产率地发生，并且感兴趣的是类似的损伤是否可以在包括核糖核苷酸和脱氧核糖核苷酸的双链体寡核苷酸中发生。构建了含有RNA和混合RNA·DNA链的组装体，其中含有拴系的乙锭作为光氧化剂。在光氧化实验中，检查了对寡核苷酸双链体的含核糖链的长程氧化损伤。空穴注入光激发的乙锭，然后自由基迁移到氧化敏感的鸟嘌呤提供了显着的损害，在长距离（约35 μ m）的核糖链。这种损伤在产量和位置上与B-DNA双链体中发现的损伤没有实质性差异。没有发现氧化损伤后，光氧化的DNA/RNA双链体含有拴系金属嵌入剂，尽管铑配合物的能力，以促进氧化损伤的距离在DNA双链体。这一结果归因于铑络合物与A样RNA/DNA双链体的偶联较差。在不同构象的双链核酸中发生长距离电荷传输的能力被认为是根据建模研究，该研究显示构成RNA/DNA杂交双链体的相对互补链之间的链间碱基-碱基重叠。因此，在转录事件的背景下，也可以考虑远程自由基迁移以影响氧化损伤或信号传导的可能性。
Oxidative damage as a result of DNA-mediated long-range charge transport occurs readily and at high yield in duplex DNA, and it is of interest whether similar damage can occur in duplex oligonucleotides that include both ribo- and deoxyribonucleotides. Assemblies containing RNA and mixed RNA·DNA strands were constructed containing tethered ethidium as a photooxidant. In photooxidation experiments, long-range oxidative damage to the ribose-containing strand of the oligonucleotide duplexes was examined. Hole injection by photoexcited ethidium followed by radical migration to oxidatively susceptible guanines afforded significant damage on ribose-containing strands at long range (∼35 Å). This damage does not differ substantially in yield and location from that found in B-DNA duplexes. No oxidative damage was found upon photooxidation of DNA/RNA duplexes containing tethered metallointercalator, despite the ability of the rhodium complex to promote oxidative damage at a distance in DNA duplexes. This result is attributed to the poor coupling of the rhodium complex into the A-like RNA/DNA duplex. The ability for long-range charge transport to occur in double-stranded nucleic acids of different comformations is considered in light of modeling studies that show interstrand base−base overlap between the opposing, complementary strands that make up RNA/DNA hybrid duplexes. Thus, the possibility of long-range radical migration to effect oxidative damage or signaling may be considered also in the context of transcriptional events.