Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage
- University of California, Berkeley, United States
- Johns Hopkins University School of Medicine, United States
Abstract
Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association in turn induces extensive DNA bending, which is needed to support duplex cleavage by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover recognition and ATP binding with strand scission, providing useful insights into the operation of type IIB topoisomerases and related meiotic recombination and GHKL ATPase machineries.
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Funding
National Institutes of Health (RO1 CA077373)
- James M Berger
National Science Foundation (DGE 1106400)
- Timothy J Wendorff
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Wendorff & Berger
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage
eLife 7:e31724.
https://doi.org/10.7554/eLife.31724
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