DNA硫化修饰的抗氧化机理研究

DNA存在一种特殊的修饰-磷硫酰化修饰。硫修饰细菌，广泛存在于土壤、海洋、人体等环境，生境各异。前期我们发现DNA骨架上的硫能与多种过氧化物发生氧化还原反应, 使硫修饰DNA具有对抗双氧水的能力, 同时赋予了细菌保护遗传核心物质DNA对抗氧化损伤的生存优势。项目拟在前期工作基础上，进一步探索DNA硫修饰抗氧化的机制问题。论证硫修饰DNA抗氧化是通过调控抗氧化的基因表达, 还是利用能够清除活性氧的化学性质。揭示硫修饰是否在DNA层面上直接起保护作用，还是作为活性氧清除体系保护其它多种生物大分子免受活性氧损伤。鉴定和阐述硫修饰DNA清除活性氧的类别及其化学机理。系统性回答这种新型的抗氧化系统是利用其自身还原性或是由酶参与的催化控制过程。项目的完成，为揭示硫修饰现象的生物学意义提供理论基础，为挖掘、利用硫修饰DNA的抗氧化功能提供线索。

DNA phosphorothioate modification, in which oxygen is swapped with sulfur in backbone, exists widely in bacteria from a variety of environment, including earth, ocean, and even in human body. We found that sulfur in the modified DNA can react with multiple oxidants, and bacterial strains endowed with phosphorothioate modification have survival advantage over the phosphorothioate negative strains.On the basis of these findings, the project will focus on elucidation of the mechanisms involving in the function of anti-oxidation of phosphorothioate DNA, answering the questions of: whether the anti-oxidation property comes from the regulation of anti-oxidation genes or the modification can function as an anti-oxidation system that can scavenge reactive oxygen species by itself. The project will further reveal whether the modification can protect DNA from oxidative damage or as a reactive oxygen species scavenge system that can protect other biological molecules, and what is the chemical basis underlying its ROS scavenging behavior. The project will also reveal whether the ROS scavenging reaction happens spontaneously or is controlled by a gene product inside a cell.The completion of the project will pave way to the full understanding of the physiological function of DNA phosphorothioate and will provide clues for its practical usage.