@article{7b387e7386ab4dc98582ebaf99ecbd8f,
title = "Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate",
abstract = "Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2{\textquoteright}s preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate.",
author = "Chen, {Shin Fu} and Huang, {Nan Lan} and Lin, {Jung Hsin} and Wu, {Chyuan Chuan} and Wang, {Ying Ren} and Yu, {Yu Jen} and Gilson, {Michael K.} and Chan, {Nei Li}",
note = "Funding Information: Portions of this research were carried out at beamlines 15A1 and 13C1 of the National Synchrotron Radiation Research Center (Taiwan), beamline SP12B2 of the SPring-8 (Japan) and the San Diego Supercomputing Center (US). We are grateful to the staffs of Technology Commons in College of Life Science and Center for Systems Biology, National Taiwan University. We thank Prof. Hung-Wen Li, Dr. Wan-Chen Huang and members of our laboratories for helpful discussion. This work was supported by the Ministry of Science and Technology (106-2113-M-002-021-MY3 and 104-2911-I-002-302 to N.-L.C.), National Taiwan University (104R7614-3 and 104R7560-4 to N.-L.C.), Academia Sinica Postdoctoral Fellowship to N.-L.H., and NIH grant GM061300 to M.K.G. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. M.K.G. has an equity interest in and is a cofounder and scientific advisor of VeraChem LLC. This paper is dedicated to the memory of Prof. Tao-shih Hsieh, a model scientist for us.",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-05406-y",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}