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STRUCTURE, MOLECULAR MECHANISMS, AND EVOLUTIONARY RELATIONSHIPS IN DNA TOPOISOMERASES

STRUCTURE, MOLECULAR MECHANISMS, AND EVOLUTIONARY RELATIONSHIPS IN DNA TOPOISOMERASES ▪ Abstract Topoisomerases are enzymes that use DNA strand scission, manipulation, and rejoining activities to directly modulate DNA topology. These actions provide a powerful means to effect changes in DNA supercoiling levels, and allow some topoisomerases to both unknot and decatenate chromosomes. Since their initial discovery over three decades ago, researchers have amassed a rich store of information on the cellular roles and regulation of topoisomerases, and have delineated general models for their chemical and physical mechanisms. Topoisomerases are now known to be necessary for the survival of cellular organisms and many viruses and are rich clinical targets for anticancer and antimicrobial treatments. In recent years, crystal structures have been obtained for each of the four types of topoisomerases in a number of distinct conformational and substrate-bound states. In addition, sophisticated biophysical methods have been utilized to study details of topoisomerase reaction dynamics and enzymology. A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Biophysics Annual Reviews

STRUCTURE, MOLECULAR MECHANISMS, AND EVOLUTIONARY RELATIONSHIPS IN DNA TOPOISOMERASES

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Publisher
Annual Reviews
Copyright
Copyright © 2004 by Annual Reviews. All rights reserved
ISSN
1936-122X
eISSN
1936-1238
DOI
10.1146/annurev.biophys.33.110502.140357
pmid
15139806
Publisher site
See Article on Publisher Site

Abstract

▪ Abstract Topoisomerases are enzymes that use DNA strand scission, manipulation, and rejoining activities to directly modulate DNA topology. These actions provide a powerful means to effect changes in DNA supercoiling levels, and allow some topoisomerases to both unknot and decatenate chromosomes. Since their initial discovery over three decades ago, researchers have amassed a rich store of information on the cellular roles and regulation of topoisomerases, and have delineated general models for their chemical and physical mechanisms. Topoisomerases are now known to be necessary for the survival of cellular organisms and many viruses and are rich clinical targets for anticancer and antimicrobial treatments. In recent years, crystal structures have been obtained for each of the four types of topoisomerases in a number of distinct conformational and substrate-bound states. In addition, sophisticated biophysical methods have been utilized to study details of topoisomerase reaction dynamics and enzymology. A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other.

Journal

Annual Review of Biophysics – Annual Reviews

Published: Jun 9, 2004

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