Differences Between Positively and Negatively Supercoiled DNA that Topoisomerases May Distinguish
Identifieur interne : 001877 ( Main/Exploration ); précédent : 001876; suivant : 001878Differences Between Positively and Negatively Supercoiled DNA that Topoisomerases May Distinguish
Auteurs : Jonathan M. Fogg [États-Unis] ; Daniel J. Catanese Jr [États-Unis] ; Graham L. Randall [États-Unis] ; Michelle C. Swick [États-Unis] ; Lynn Zechiedrich [États-Unis]Source :
- The IMA Volumes in Mathematics and its Applications [ 0940-6573 ]
Abstract
Abstract: In all living cells, DNA is homeostatically underwound relative to its lowest energy conformation, resulting in egative supercoiling. This underwinding of DNA is critical to the metabolism of DNA and, thus, is vital to cell survival. Enzymes called topoisomerases regulate and maintain the supercoiled state of DNA and are critical to the successful replication of the genome. These enzymes are major targets for drugs used in the treatment of bacterial infections and cancer. One puzzling phenomenon of the topoisomerase mechanism is how these enzymes, orders of magnitude smaller than their substrate, can search, recognize and act at a local level to affect global DNA topology. While the homeostatic state of DNA supercoiling in cells is negative, both positive and negative supercoils exist transiently. Because of the right-handed nature of the DNA helix, the positive and negative supercoils are not equivalent. Several computational and theoretical models have been developed in an effort to describe the features of both positively and negatively supercoiled DNA. These models have accurately predicted some of the phenomena observed in vivo. However, the over-simplifying assumptions cannot account for the different biological activities of positively and negatively supercoiled DNA. This review will discuss the models in place and the mathematical and energetic properties of this elegant molecule and the “machines that push it around.”
Url:
DOI: 10.1007/978-1-4419-0670-0_5
Affiliations:
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<front><div type="abstract" xml:lang="en">Abstract: In all living cells, DNA is homeostatically underwound relative to its lowest energy conformation, resulting in egative supercoiling. This underwinding of DNA is critical to the metabolism of DNA and, thus, is vital to cell survival. Enzymes called topoisomerases regulate and maintain the supercoiled state of DNA and are critical to the successful replication of the genome. These enzymes are major targets for drugs used in the treatment of bacterial infections and cancer. One puzzling phenomenon of the topoisomerase mechanism is how these enzymes, orders of magnitude smaller than their substrate, can search, recognize and act at a local level to affect global DNA topology. While the homeostatic state of DNA supercoiling in cells is negative, both positive and negative supercoils exist transiently. Because of the right-handed nature of the DNA helix, the positive and negative supercoils are not equivalent. Several computational and theoretical models have been developed in an effort to describe the features of both positively and negatively supercoiled DNA. These models have accurately predicted some of the phenomena observed in vivo. However, the over-simplifying assumptions cannot account for the different biological activities of positively and negatively supercoiled DNA. This review will discuss the models in place and the mathematical and energetic properties of this elegant molecule and the “machines that push it around.”</div>
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