Theoretical Study on Repair Mechanisms of DNA Damages

当DNA暴露于波长约260 nm的辐射时，相邻的嘧啶通过各自C5饱和而形成四元环结构而形成共价连接。C6双键。通过这种光化学环加成形成的结构被称为嘧啶二聚体。本研究采用HF、CASSCF和dft方法研究了嘧啶二聚体的结构，并用CASSCF方法研究了嘧啶二聚体的裂解过程，并采用分子动力学方法研究了嘧啶二聚体与DNA的构象变化，发现嘧啶二聚体的dft结构与HF和CASSCF结构非常接近。在C5和C6原子处的环融合导致褶皱的四元环丁烷环。环丁烷环中的四个键和四个角几乎相等。环丁烷环上的取代基原子的褶皱具有轴向或赤道方向：两个嘧啶碱基上的相应原子的方向性不同。电离后，C6-C6'键变得很长，相当于只有一个电子的键。CASSCF水平上的计算表明，胸腺嘧啶二聚体自由基阳离子的断裂反应是一个逐步的过程，一旦从胸腺嘧啶二聚体中除去一个电子，就可以很容易地以低的能垒进行。胸腺嘧啶二聚体中四元环的褶皱决定了电子沿着断裂运动的方向。考虑到嘧啶二聚体的分子环境（DNA和溶剂环境），进行了分子动力学模拟。

When DNA is exposed to radiation at wavelengths of about 260 nm, adjacent phyrimidines become covalently linked by the formation of a four-member ring structure resulting from the saturation of their respective C5 . C6 double bonds. The structure formed by this photochemical cycloaddition is referred to as a pyrimidine dimer. In this study, we investigated 1) the structures of the homo- and hetero-pyrimidine dimers by means of HF, CASSCF and dft methods and the process of the dimer splitting by means of CASSCF method, and 2) the conformational change of DNA with pyrimidine dimer by means of molecular dynamics.It is found that the dft structure of pyrimidine dimer is very close to the HF and CASSCF structures. T, he ring fusion at the C5 and C6 atoms leads to the puckered four-member cyclobutane ring. The four bonds and the four angles in the cyclobutane ring are almost equal. The puckering has axial or equatorial directions for the substituent atoms on the cyclobutane ring: corresponding atoms on the two pyrimidine bases differ in directionality. Upon ionization, the C6-C6' bond becomes very long, corresponding to a bond with only one electron. Calculations at the level of CASSCF indicate that the fragmentation reaction of the thymine dimer radical cation is a stepwise process and may proceed easily with low energy barriers once an electron is removed from the thymine dimer. The puckering of the four-member ring in the thymine dimer determines the direction of the electron movement along the fragmentation. Taking account of the molecular environment of pyrimidine dimer (DNA and solvent environments) , the molecular dynamics simulations have been performed.