DNA DAMAGE STUDIED BY ULTRAFAST SPECTROSCOPY

核酸和其他生物分子的激发电子态 是几乎所有形式的辐射损害的前驱 遗传物质。目前人们对这些前驱状态知之甚少。 因为它们在生理温度下寿命极短， S的寿命在10-13到10-11的数量级。拟议的研究将使用 直接研究核酸的最新超快方法 紫外光激发的状态会导致表面上的损伤 核苷酸螺旋。我们的目标是确定如何激发/损害 过程取决于碱基含量和螺旋的构象，螺旋的方式 插层剂可以截获沉积在螺旋上的能量，并 在没有核苷酸损伤的情况下耗散能量，以及为什么大多数损害 位点似乎涉及嘧啶二聚体和加合物。主要的方法是 使用的是时间和波长分辨的吸收和荧光 使用定义明确的合成核苷酸低聚物和聚合物的光谱学 旨在回答有关损坏机制的具体问题。这些 研究将首次直接探索宇宙的时间演化。 由紫外线吸收引起的主要能量事件和将 量化DNA中能量配置的速度和途径，从而导致 基地损毁。

Excited electronic states of nucleic acids and other biological molecules are the precursors of virtually all forms of radiation damage to the genetic material. These precursor states are poorly understood at present because they are extremely short-lived at physiological temperatures, with lifetimes on the order of 10-13 to 10-11 s. The research proposed will use state-of-the-art ultrafast methods to directly study the nucleic acid states excited by ultraviolet light which lead to damage sties on the nucleotide helix. The goals are to determine how the excitation/damage process depends upon base content and conformation of the helix, how helix intercalating agents can intercept energy deposited on the helix and dissipate the energy without nucleotide damage, and why most of the damage sites seems to involve pyrimidine dimers and adducts. The primary methods to be used are time- and wavelength-resolved absorption and fluorescence spectroscopy using well-defined synthetic nucleotide oligomers and polymers designed to answer specific questions concerning damage mechanisms. These studies will for the first time directly probe the time evolution of the major energetic events caused by ultraviolet light absorption and will quantitate rates and routes of energy disposition in DNA which leads to base damage.