Probing DNA Structure by Photoelectron Transter and Its Application toward Gene The rapy

DNA构象在DNA功能的几乎所有方面都起着重要作用，包括DNA复制、基因表达和调控。了解DNA构象及其在生物过程中的作用是当前的研究热点，它将为设计新的抗癌和基因治疗药物提供有价值的信息。本研究的目的是评价5-氟尿嘧啶光反应作为DNA局部构象分析和构象特异性DNA裂解剂的潜力。研究发现，含溴酸(Bru)的寡核苷酸能有效地在ABrU序列的腺嘌呤残基上产生脱氧核糖1‘氧化产物，而含碘(Iu)的寡聚体则能产生相当数量的1’和2‘氧化产物。阐明了氧化DNA链断裂的详细机制，包括1，2-氢化物在1‘氧化产物形成过程中的移动。ABrU光化学单元被引入到各种类型的DNA构象中。结果表明，A构象提高了反应效率，提高了1‘氧化反应的特异性。腺嘌呤位错配的引入不会改变光反应性，而Bru位错配的引入大大降低了光反应性。

DNA conformation plays an important role in nearly every aspect of DNA function, including DNA replication, gene expression and regulation. Understanding DNA conformation and its role in biological processes is intense current interest and it will be a valuable information in designing new anticancer and gene-thepeutic agents. The aim of this research is to evaluate the potential of 5-halouracil photoreaction as DNA local conformational analysis and conformation-specific DNA cleaving agent. It was found that photoiradiation of bromouracil (BrU) -containing oligonucleotide efficiently produces deoxyribose 1' oxidation product at adenine residue of ABrU Sequence, while iodoracil (IU) -containing oligomer produces comparable amount of 1' and 2' oxidation products. Detailed mechanism of oxidative DNA strand scission including 1,2-hydride shift in the formation of 1' oxidation product was elucidated. ABrU photochemical unit was introduced into various type of DNA conformations. It was found that A conformation enhanced efficiency of the reaction and specificity of 1' oxidation was increased. Introduction of mismatch at adenine site does not change the photoreactivity whereas introduction of mismatch at BrU site greatly reduced photoreactivity.