DNA结合蛋白在DNA上的易化扩散及特异位点搜寻机制的单分子生物物理研究

项目名称： DNA结合蛋白在DNA上的易化扩散及特异位点搜寻机制的单分子生物物理研究

项目编号： No.31270803

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 苏晓东

作者单位： 北京大学

项目金额： 90万元

中文摘要： 各种不同功能及结构类型的DNA结合蛋白都需要很快找到其DNA上的特定结合位点而行使功能。 蛋白质对DNA上特定位点的结合及搜寻一般认为需要经历三维扩散结合到DNA的非特异位点，然后沿着DNA双螺旋链一维搜寻结合位点这两种过程（所谓易化扩散）有效结合来实现。 三维扩散主要由细胞质内的热运动控制，而一维搜寻则是个复杂的过程，一般认为包括非特异性一维扩散及沿DNA的滑行。 不同功能的DNA结合蛋白在DNA上的一维扩散机制可能很不相同。 要全面系统地深入了解DNA-蛋白质的非特异性结合及对特异性位点的搜寻，必须对许多不同结构及功能的DNA结合蛋白进行系统的单分子生物物理研究。 本课题旨在通过单分子生物物理实验及理论建模研究多种（100种以上）结构类型及不同功能的DNA结合蛋白在DNA上的一维易化扩散机制，从而归纳总结出具有普遍意义的，系统全面的DNA-蛋白质相互作用机制及位点搜寻模型。

中文关键词： 搜寻机制;；易化扩散;；单分子;；微流控制;；一维扩散

英文摘要： For many DNA-binding proteins to efficiently achieve their function, it is essential to be able to rapidly search for the specific target DNA sites. In searching for a target DNA sequence, a DNA binding protein such as transcription factors, DNA repair proteins etc. first will non-specifically bind to the DNA, then undergo 1-D diffusion along a short segment of DNA before dissociating from DNA, diffusion in 3-D through the cytoplasm, and rebinding to a different DNA segment again, and this process repeats itself many times until the target sites to be found. The 3-D diffusion is driven by the thermal motion, but the 1-D diffusion is much more complicated. It has been shown that proteins can both hop and slide along double-stranded DNA, as well as DNA-binding proteins undergo rotation-coupled sliding along the DNA double helix. So, proteins with different function and structures will likely undergo different mechanisms in 1-D diffusion on DNA. So far, however, only a handful of DNA-binding proteins have been investigated about their 1-D non-specific binding despite hundreds if not thousands of different DNA-binding proteins have been identified. In this applying project, we are going to study the mechanisms of many different types (up to 100) of DNA binding proteins for their non-specific binding on DNA, espe

英文关键词： Search-mechanism;；Facilitated diffusion;；Single-molecule;；Flow-stretching;；1D diffusion