Redox Photochemistry of Oxidized Bases in DNA and RNA

DNA 和 RNA 中氧化碱基的氧化还原光化学

• 批准号: 1152533
• 负责人: Cynthia Burrows
• 金额: $ 48.8万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1152533&HistoricalAwards=false
• 关键词: Redox; Photochemistry; Oxidized; Bases; DNA

With this award, the Chemistry of Life Processes Program is supporting the research of Professor Cynthia Burrows of the University of Utah. Professor Burrows hypothesizes that simple chemical transformations of RNA bases could have been the key steps in creating redox active catalysts driving early chemical systems toward a primitive metabolism. With prior NSF funding, her laboratory has shown that the oxidized base 8-oxoguanine serves as a photochemical catalyst to reductively reverse cyclobutane pyrimidine dimers to monomers. In this reaction, 8-oxoguanine acts as a flavin mimic to facilitate excited state electron transfer. Future work will explore 8-oxopurines and other redox active RNA purine and pyrimidine base derivatives for their ability to mediate oxidation and reduction reactions. For example, key reactions of early Earth must have included the ability to interconvert alcohols and aldehydes or ketones (e.g. lactate/pyruvate) using redox cofactors analogous to NADH and FADH2. Reactions such as these will be studied in RNA world-like conditions in order to test the hypothesis that simpler versions of these RNA-based cofactors could have presaged modern-day metabolism.The broader impacts of this project are demonstrated in the unusual link between DNA damage and repair chemistry pertinent to cancer and the chemistry of primordial Earth. Photoinduced electron transfer appears to play a role in both realms, and insights from this work could be broadly applicable to other disciplines. Students trained on the project will be involved in interdisciplinary sciences including aspects of synthetic and physical organic, analytical and biochemistry. Professor Burrows has demonstrated continuing leadership in broadening participation, including programs that advance the careers of women scientists, and will continue to be active in dissemination of research to public audiences.

有了这个奖项，《生命过程》计划的化学计划正在支持犹他大学辛西娅·伯罗斯教授的研究。 Burrows教授假设RNA碱基的简单化学转化可能是创建氧化还原活性催化剂的关键步骤，将早期化学系统推向原始代谢。 通过先前的NSF资助，她的实验室表明，氧化的碱基8-氧气烷氨酸可作为光化学催化剂，可将细胞单丁烷嘧啶二聚体还原为单体。 在此反应中，8-氧气甘氨酸充当黄素模仿，以促进激发态电子转移。 未来的工作将探索8-氧化剂和其他氧化还原活性RNA嘌呤和嘧啶碱衍生物的介导氧化和还原反应的能力。 例如，早期地球的关键反应必须包括使用类似于NADH和FADH2的氧化还原辅助因子互连醇和醛或酮（例如乳酸/丙酮酸）的能力。 将在类似RNA世界的条件下进行研究，以检验以下假设：这些基于RNA的辅助因子的更简单版本可以预示现代代谢。该项目的更广泛影响在DNA损伤与修复化学之间的不寻常联系中证明了与癌症与原始地球的化学相关的联系。 光诱导的电子转移似乎在两个领域都起作用，这项工作的见解可能广泛适用于其他学科。 接受该项目培训的学生将参与跨学科科学，包括合成和物理有机，分析和生物化学方面。 Burrows教授表现出在扩大参与方面的持续领导才能，包括推进女性科学家职业的计划，并将继续积极地向公众观众传播研究。