Kamagata Kiyoto
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Japan.
Front Mol Biosci. 2021 Nov 19;8:795367. doi: 10.3389/fmolb.2021.795367. eCollection 2021.
DNA-binding proteins trigger various cellular functions and determine cellular fate. Before performing functions such as transcription, DNA repair, and DNA recombination, DNA-binding proteins need to search for and bind to their target sites in genomic DNA. Under evolutionary pressure, DNA-binding proteins have gained accurate and rapid target search and binding strategies that combine three-dimensional search in solution, one-dimensional sliding along DNA, hopping and jumping on DNA, and intersegmental transfer between two DNA molecules. These mechanisms can be achieved by the unique structural and dynamic properties of these proteins. Single-molecule fluorescence microscopy and molecular dynamics simulations have characterized the molecular actions of DNA-binding proteins in detail. Furthermore, these methodologies have begun to characterize liquid condensates induced by liquid-liquid phase separation, e.g., molecular principles of uptake and dynamics in droplets. This review discusses the molecular action of DNA-binding proteins on DNA and in liquid condensate based on the latest studies that mainly focused on the model protein p53.
DNA结合蛋白引发各种细胞功能并决定细胞命运。在执行转录、DNA修复和DNA重组等功能之前，DNA结合蛋白需要在基因组DNA中搜索并结合其靶位点。在进化压力下，DNA结合蛋白获得了精确且快速的靶标搜索和结合策略，这些策略结合了在溶液中的三维搜索、沿DNA的一维滑动、在DNA上的跳跃以及两个DNA分子之间的片段间转移。这些机制可通过这些蛋白质独特的结构和动力学特性来实现。单分子荧光显微镜和分子动力学模拟已详细表征了DNA结合蛋白的分子作用。此外，这些方法已开始表征由液-液相分离诱导的液体凝聚物，例如液滴中摄取和动力学的分子原理。本综述基于主要聚焦于模型蛋白p53的最新研究，讨论了DNA结合蛋白在DNA上以及在液体凝聚物中的分子作用。
