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Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective

Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that perform important intracellular roles in chromosome condensation and segregation, and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase, is a homodimeric enzyme that solves topological entanglement...

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Detalles Bibliográficos
Autores principales: Collins, Tammy R. L., Hammes, Gordon G., Hsieh, Tao-shih
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647300/
https://www.ncbi.nlm.nih.gov/pubmed/19155278
http://dx.doi.org/10.1093/nar/gkn1059
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author Collins, Tammy R. L.
Hammes, Gordon G.
Hsieh, Tao-shih
author_facet Collins, Tammy R. L.
Hammes, Gordon G.
Hsieh, Tao-shih
author_sort Collins, Tammy R. L.
collection PubMed
description Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that perform important intracellular roles in chromosome condensation and segregation, and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase, is a homodimeric enzyme that solves topological entanglement problems by using the energy from ATP hydrolysis to pass one segment of DNA through another by way of a reversible, enzyme-bridged double-stranded break. This DNA break is linked to the protein by a phosphodiester bond between the active site tyrosine of each subunit and backbone phosphate of DNA. The opening and closing of the DNA gate, a critical step for strand passage during the catalytic cycle, is coupled to this enzymatic cleavage/religation of the backbone. This reversible DNA cleavage reaction is the target of a number of anticancer drugs, which can elicit DNA damage by affecting the cleavage/religation equilibrium. Because of its clinical importance, many studies have sought to determine the manner in which topo II interacts with DNA. Here we highlight recent single-molecule fluorescence resonance energy transfer and crystallographic studies that have provided new insight into the dynamics and structure of the topo II DNA gate.
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spelling pubmed-26473002009-03-04 Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective Collins, Tammy R. L. Hammes, Gordon G. Hsieh, Tao-shih Nucleic Acids Res Survey and Summary Type II DNA topoisomerases (topos) are essential and ubiquitous enzymes that perform important intracellular roles in chromosome condensation and segregation, and in regulating DNA supercoiling. Eukaryotic topo II, a type II topoisomerase, is a homodimeric enzyme that solves topological entanglement problems by using the energy from ATP hydrolysis to pass one segment of DNA through another by way of a reversible, enzyme-bridged double-stranded break. This DNA break is linked to the protein by a phosphodiester bond between the active site tyrosine of each subunit and backbone phosphate of DNA. The opening and closing of the DNA gate, a critical step for strand passage during the catalytic cycle, is coupled to this enzymatic cleavage/religation of the backbone. This reversible DNA cleavage reaction is the target of a number of anticancer drugs, which can elicit DNA damage by affecting the cleavage/religation equilibrium. Because of its clinical importance, many studies have sought to determine the manner in which topo II interacts with DNA. Here we highlight recent single-molecule fluorescence resonance energy transfer and crystallographic studies that have provided new insight into the dynamics and structure of the topo II DNA gate. Oxford University Press 2009-02 2009-01-20 /pmc/articles/PMC2647300/ /pubmed/19155278 http://dx.doi.org/10.1093/nar/gkn1059 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Survey and Summary
Collins, Tammy R. L.
Hammes, Gordon G.
Hsieh, Tao-shih
Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title_full Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title_fullStr Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title_full_unstemmed Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title_short Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective
title_sort analysis of the eukaryotic topoisomerase ii dna gate: a single-molecule fret and structural perspective
topic Survey and Summary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647300/
https://www.ncbi.nlm.nih.gov/pubmed/19155278
http://dx.doi.org/10.1093/nar/gkn1059
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