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Untangling the Double Helix
DNA Entanglement and the Action of the DNA Topoisomerases

Subject Area(s):  Molecular BiologyBiochemistryBiophysics

By James C. Wang, Harvard University

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© 2009 • 233 pp., illus., appendices, index
Paperback •
ISBN  978-087969879-9

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The problem of unraveling two intertwined strands during the duplication of DNA was recognized shortly after the proposal of the DNA double helix structure in 1953. A group of enzymes called DNA topoisomerases solve this problem by breaking and rejoining DNA molecules in a controlled manner, thereby allowing strands to be passed through each other and thus untangled—not just during DNA replication, but also during many other basic cellular processes. Because of their intimate involvement in the workings of the cell, topoisomerases are also the logical targets of many antibiotics (including Cipro) and anticancer agents.

This book, written by James Wang, the discoverer of the first topoisomerase and a leader in the field since, presents ten chapters covering the historical backdrop of the DNA entanglement problem and the discovery of the DNA topoisomerases, how DNA topoisomerases perform their magic in DNA replication, transcription, genetic recombination and chromosome condensation, and how they are targets of therapeutic agents. The book should appeal to readers from undergraduates upwards with interests in the biological and clinical aspects of topoisomerase function, or in the mathematics and physics of topology.


1. An Insuperable Problem
2. Nature's Solutions: The DNA Topoisomerases
3. Breaking a DNA Strand and Holding on to the Broken Ends
4. A Magic Swivel
5. Moving One DNA Double Helix through Another
6. Real-Time Viewing of the DNA Topoisomerases in Action
7. Manifestations of DNA Entanglement: Replication and Recombination
8. Manifestations of DNA Entanglement: Gene Expression
9. Beyond DNA Entanglement: New Twists on an Old Theme
10. From Nature's Battlefields to the Clinical Wards
1. Identification of the Covalent Intermediates in Topoisomerase-Catalyzed Reactions
2. Catalysis of DNA Breakage and Rejoining by DNA Topoisomerases


review:  ”In Untangling the Double Helix, Wang offers a very accessible and thorough introduction to DNA topoisomerases, from their basic properties to their roles in biology and medicine. The author ’s important contributions to the development of the field allow him to provide a lively account of the discovery and subsequent characterization of this family of enzymes. The book is enjoyable and easy to follow, with clear illustrations to help explain several major points...

The book successfully aims at a general audience not necessarily familiar with topoisomerases or their biology. Anyone wishing to learn more about these enzymes or some of the ideas behind their discovery will find Wang ’s account illuminating. It makes a perfect companion to textbooks in biochemistry or molecular biology, demonstrating the advantage of presenting not only the facts but also the always interesting backgrounds to important discoveries.”

review:  “Untangling the Double Helix tells a highly stylized story that is marked by a clarity of thought and expression. Its goal is not to be a comprehensive volume that encompasses every aspect of topoisomerases. Rather, it serves as a well-written, often personal overview of the field. As a result, this engaging publication occupies a unique niche in the world of topoisomerases. It contains enough detail to make it a welcome addition to the bookshelves of investigators in the field, yet it is sufficiently accessible to serve as a superb introduction for those who are not yet acquainted with these fascinating enzymes.”
      —The Quarterly Review of Biology

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