Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate

Shin-Fu Chen, Nan-Lan Huang, Jung-Hsin Lin, Chyuan-Chuan Wu, Ying-Ren Wang, Yu-Jen Yu, Michael K. Gilson () and Nei-Li Chan ()
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Shin-Fu Chen: College of Medicine, National Taiwan University
Nan-Lan Huang: Research Center for Applied Sciences and Institute of Biomedical Sciences, Academia Sinica
Jung-Hsin Lin: Research Center for Applied Sciences and Institute of Biomedical Sciences, Academia Sinica
Chyuan-Chuan Wu: College of Medicine, National Taiwan University
Ying-Ren Wang: College of Medicine, National Taiwan University
Yu-Jen Yu: College of Medicine, National Taiwan University
Michael K. Gilson: University of California, San Diego
Nei-Li Chan: College of Medicine, National Taiwan University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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’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.

Date: 2018
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DOI: 10.1038/s41467-018-05406-y

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