Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA

Yunsu Jang; Heyjin Son; Sang Wook Lee; Wonseok Hwang; Seung Ryoung Jung; Jo Ann W. Byl; Neil Osheroff; Sanghwa Lee

doi:10.1016/j.chembiol.2018.12.003

Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA

Yunsu Jang, Heyjin Son, Sang Wook Lee, Wonseok Hwang, Seung Ryoung Jung, Jo Ann W. Byl, Neil Osheroff, Sanghwa Lee

Department of Artificial Intelligence

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Topoisomerase II cleaves DNA at preferred sequences with different efficiencies; however, the mechanism of cleavage site selection is not known. Here we used single-molecule fluorescence assays that monitor several critical steps of DNA-topoisomerase II interactions, including binding/dissociation, bending/straightening, and cleavage/religation, and reveal that the cleavage site is selected mainly during the bending step. Furthermore, despite the sensitivity of the bending rate to the DNA sequence, it is not an intrinsic property of the DNA itself. Rather, it is determined by protein-DNA interactions.

Original language	English
Pages (from-to)	502-511.e3
Journal	Cell Chemical Biology
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.chembiol.2018.12.003
State	Published - 18 Apr 2019

Keywords

DNA bending
DNA cleavage
DNA flexibility
G-segment selection
sequence preference
single-molecule FRET
topoisomerase II
two-metal-ion mechanism

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10.1016/j.chembiol.2018.12.003

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title = "Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA",

abstract = "Topoisomerase II cleaves DNA at preferred sequences with different efficiencies; however, the mechanism of cleavage site selection is not known. Here we used single-molecule fluorescence assays that monitor several critical steps of DNA-topoisomerase II interactions, including binding/dissociation, bending/straightening, and cleavage/religation, and reveal that the cleavage site is selected mainly during the bending step. Furthermore, despite the sensitivity of the bending rate to the DNA sequence, it is not an intrinsic property of the DNA itself. Rather, it is determined by protein-DNA interactions.",

keywords = "DNA bending, DNA cleavage, DNA flexibility, G-segment selection, sequence preference, single-molecule FRET, topoisomerase II, two-metal-ion mechanism",

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AU - Jang, Yunsu

AU - Son, Heyjin

AU - Lee, Sang Wook

AU - Hwang, Wonseok

AU - Jung, Seung Ryoung

AU - Byl, Jo Ann W.

AU - Osheroff, Neil

AU - Lee, Sanghwa

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N2 - Topoisomerase II cleaves DNA at preferred sequences with different efficiencies; however, the mechanism of cleavage site selection is not known. Here we used single-molecule fluorescence assays that monitor several critical steps of DNA-topoisomerase II interactions, including binding/dissociation, bending/straightening, and cleavage/religation, and reveal that the cleavage site is selected mainly during the bending step. Furthermore, despite the sensitivity of the bending rate to the DNA sequence, it is not an intrinsic property of the DNA itself. Rather, it is determined by protein-DNA interactions.

AB - Topoisomerase II cleaves DNA at preferred sequences with different efficiencies; however, the mechanism of cleavage site selection is not known. Here we used single-molecule fluorescence assays that monitor several critical steps of DNA-topoisomerase II interactions, including binding/dissociation, bending/straightening, and cleavage/religation, and reveal that the cleavage site is selected mainly during the bending step. Furthermore, despite the sensitivity of the bending rate to the DNA sequence, it is not an intrinsic property of the DNA itself. Rather, it is determined by protein-DNA interactions.

KW - DNA bending

KW - DNA cleavage

KW - DNA flexibility

KW - G-segment selection

KW - sequence preference

KW - single-molecule FRET

KW - topoisomerase II

KW - two-metal-ion mechanism

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Selection of DNA Cleavage Sites by Topoisomerase II Results from Enzyme-Induced Flexibility of DNA

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