Topoisomerase VI is a chirally-selective, preferential DNA decatenase.
Topoisomerase VI is a chirally-selective, preferential DNA decatenase.
复制标题
DOI：
10.7554/elife.67021
复制
发表时间：
2022-01-25
期刊：
影响因子：
7.7
通讯作者：
Neuman KC
中科院分区：
文献类型：
--
作者：
McKie SJ;Desai PR;Seol Y;Allen AM;Maxwell A;Neuman KC
DNA拓扑异构酶VI（英语：DNA topoisomerase VI）是一种IIB型DNA拓扑异构酶，主要存在于古细菌和一些细菌中，但也存在于植物和藻类中。自其发现以来，拓扑异构酶VI已被提出是一种DNA脱连环酶;然而，缺乏强有力的证据和其优先脱连环活性的机制。使用单分子磁镊测量和支持合奏生物化学，我们表明，Methanosarcina Mazei拓扑VI优先unlinks，或decatenates DNA交叉，相比放松超螺旋，通过偏好某些DNA交叉几何形状。此外，topo VI显示出ATP酶活性、DNA结合和链通过速率随着DNA扭动的增加而显著增加，这进一步证明topo VI是DNA交叉传感器。我们的研究有力地表明，拓扑VI已经进化出一种内在的偏好，通过感知和优先解开几何形状接近90°的DNA交叉，解开和解开相互连接的染色体。
DNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase; however, robust evidence and a mechanism for its preferential decatenation activity was lacking. Using single-molecule magnetic tweezers measurements and supporting ensemble biochemistry, we demonstrate that Methanosarcina mazei topo VI preferentially unlinks, or decatenates DNA crossings, in comparison to relaxing supercoils, through a preference for certain DNA crossing geometries. In addition, topo VI demonstrates a significant increase in ATPase activity, DNA binding and rate of strand passage, with increasing DNA writhe, providing further evidence that topo VI is a DNA crossing sensor. Our study strongly suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90°.