Seol Yeonee, Neuman Keir C
Laboratory of Single Molecule Biophysics, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, 50 South Dr., Room 3517, Bethesda, MD, 20892, USA.
Biophys Rev. 2016 Nov;8(Suppl 1):101-111. doi: 10.1007/s12551-016-0240-8. Epub 2016 Nov 14.
Topological properties of DNA influence its structure and biochemical interactions. Within the cell, DNA topology is constantly in flux. Transcription and other essential processes, including DNA replication and repair, not only alter the topology of the genome but also introduce additional complications associated with DNA knotting and catenation. These topological perturbations are counteracted by the action of topoisomerases, a specialized class of highly conserved and essential enzymes that actively regulate the topological state of the genome. This dynamic interplay among DNA topology, DNA processing enzymes, and DNA topoisomerases is a pervasive factor that influences DNA metabolism in vivo. Building on the extensive structural and biochemical characterization over the past four decades that has established the fundamental mechanistic basis of topoisomerase activity, scientists have begun to explore the unique roles played by DNA topology in modulating and influencing the activity of topoisomerases. In this review we survey established and emerging DNA topology-dependent protein-DNA interactions with a focus on in vitro measurements of the dynamic interplay between DNA topology and topoisomerase activity.
DNA的拓扑性质影响其结构和生化相互作用。在细胞内,DNA拓扑结构不断变化。转录和其他重要过程,包括DNA复制和修复,不仅会改变基因组的拓扑结构,还会引入与DNA打结和连环相关的额外复杂性。这些拓扑扰动可通过拓扑异构酶的作用来抵消,拓扑异构酶是一类高度保守且必不可少的特殊酶,可积极调节基因组的拓扑状态。DNA拓扑结构、DNA加工酶和DNA拓扑异构酶之间的这种动态相互作用是影响体内DNA代谢的一个普遍因素。基于过去四十年来广泛的结构和生化特征研究,这些研究已确立了拓扑异构酶活性的基本机制基础,科学家们开始探索DNA拓扑结构在调节和影响拓扑异构酶活性方面所发挥的独特作用。在本综述中,我们将概述已确立的和新出现的依赖于DNA拓扑结构的蛋白质-DNA相互作用,重点关注DNA拓扑结构与拓扑异构酶活性之间动态相互作用的体外测量。