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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。
Abstract：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 protein/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 of a 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.
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基本信息:
中图分类号:Q523
引用信息:
[1]唐志姣,刘芳,王呈坤,等.化学交联法在DNA损伤和修复机制研究中的应用[J].基因组学与应用生物学,2013,32(03):393-398.
基金信息:
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
2013-06-28
2013-06-28