化学交联法在DNA损伤和修复机制研究中的应用  

The Application of Chemical Crosslinking in the Mechanism Study of DNA Damage and Repair

作　　者：唐志姣[1,2] 刘芳[1,2] 王呈坤[2] 龚福春[1] 

机构地区：[1]长沙理工大学化学与生物工程学院,长沙410114 [2]中国科学院上海有机化学研究所生命有机化学国家重点实验室,上海200032

出　　处：《基因组学与应用生物学》2013年第3期393-398,共6页Genomics and Applied Biology

基　　金：卫生部重大新药创制专项-重组蛋白和抗体库研制平台(2011ZX09506);科技部"蛋白质重大研究计划"(2009CB918600;2011CB966300)共同资助

摘　　要：DNA分子在生物体内受到物理、化学等因素的影响,如X-射线和药物,会发生不同程度与类型的碱基损伤,诱发基因突变或细胞损害,引发包括癌症在内的各种疾病。因此研究DNA损伤与修复机制至关重要。但在DNA损伤修复机制研究过程中,目前最大的困难在于如何有效架构碱基损伤的DNA与用于修复DNA损伤修复酶的瞬态复合物,以探讨这些酶如何特异性识别损伤位点。本文综述利用化学交联法通过二硫键的方式实现酶与碱基损伤的DNA瞬态复合物的形成的相关研究进展,以期为其它DNA损伤或DNA碱基化学修饰机制研究提供参考。Cellular DNA is constantly subjected to modifications by intracellular and extracellular chemicals, which can result in all kinds of damage, and then cause various diseases including cancer. To understand pro-tein/DNA interactions and the damage repair mechanism, a structure of the protein/DNA complex is desirable. However, transient protein/DNA complexes are almost impossible to obtain for structural studies using traditional methods for several reasons. In this paper, a detail review on the research progress that previous studies have used disulfide crosslinking to trap distinct structural states ofa protein/DNA interaction, especially on known direct DNA repair proteins, which are engaged in alkylation DNA damage repair. This method, an equilibrium process that relies on protein/DNA interactions, enables us to trap and isolate homogeneous protein/DNA complexes for structural characterization.

关 键 词：化学交联法 DNA损伤 DNA修复 二硫键 

分 类 号：Q523[生物学—生物化学]