Faraji Shirin, Dreuw Andreas
Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, 69120 Heidelberg, Germany; email:
Annu Rev Phys Chem. 2014;65:275-92. doi: 10.1146/annurev-physchem-040513-103626. Epub 2013 Dec 16.
DNA photolyases are light-activated enzymes that repair DNA damage induced by ultraviolet (UV) radiation. UV radiation causes two of the most abundant mutagenic and cytotoxic DNA lesions: cyclobutane pyrimidine dimers and 6-4 photolesions. Photolyases selectively bind to DNA and initiate the splitting of mutagenic pyrimidine dimers via photoinduced electron transfer from a flavin adenine dinucleotide anion (FADH(-)) to the lesion triggering its repair. This review discusses the consecutive steps of the repair process, from both experimental and theoretical points of view. It covers the following issues: the process of how photolyases accommodate the lesion into their binding pockets, excitation energy transfer between two involved catalytic cofactors, photoinduced electron transfer to the lesion, the splitting of the pyrimidine dimer radical anion, and the fate of the unstable radical species created after the splitting of the thymine dimer. In particular, mechanisms of the splitting and restoration of the original bases are described in detail, and the most probable repair pathways are outlined.
DNA光解酶是一种光激活酶，可修复由紫外线（UV）辐射诱导的DNA损伤。紫外线辐射会导致两种最常见的诱变和细胞毒性DNA损伤：环丁烷嘧啶二聚体和6-4光损伤。光解酶选择性地与DNA结合，并通过从黄素腺嘌呤二核苷酸阴离子（FADH(-)）到损伤部位的光诱导电子转移引发诱变嘧啶二聚体的分裂，从而触发其修复。本综述从实验和理论两个角度讨论了修复过程的连续步骤。它涵盖以下问题：光解酶如何将损伤部位容纳到其结合口袋中的过程、两个相关催化辅因子之间的激发能量转移、向损伤部位的光诱导电子转移、嘧啶二聚体自由基阴离子的分裂以及胸腺嘧啶二聚体分裂后产生的不稳定自由基物种的命运。特别详细描述了原始碱基的分裂和恢复机制，并概述了最可能的修复途径。
