Theoretical Study on Repair Mechanisms of DNA Damages

点击翻译按钮获取中文摘要

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.