National Academies Press: OpenBook

Calculating the Secrets of Life: Contributions of the Mathematical Sciences to Molecular Biology (1995)

Chapter: Chapter 6 Winding the Double Helix: Using Geometry, Topology, and Mechanics of DNA

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Suggested Citation:"Chapter 6 Winding the Double Helix: Using Geometry, Topology, and Mechanics of DNA ." National Research Council. 1995. Calculating the Secrets of Life: Contributions of the Mathematical Sciences to Molecular Biology. Washington, DC: The National Academies Press. doi: 10.17226/2121.
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Page 153
Suggested Citation:"Chapter 6 Winding the Double Helix: Using Geometry, Topology, and Mechanics of DNA ." National Research Council. 1995. Calculating the Secrets of Life: Contributions of the Mathematical Sciences to Molecular Biology. Washington, DC: The National Academies Press. doi: 10.17226/2121.
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Page 154

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WINDING THE DOUBLE HELIX: USING GEOMETRY, TOPOLOGY, AND MECHANICS OF DNA 153 Chapter 6— Winding the Double Helix: Using Geometry, Topology, and Mechanics of DNA James H. White University of California, Los Angeles Crick and Watson's double helix model describes the local structure of DNA, but the global structure is more complex. The DNA double helix follows an axis that is typically curved—creating a phenomenon called supercoiling, which is crucial for a wide variety of biological processes. Understanding supercoiling requires ideas from geometry and topology. In this chapter, the author discusses three key descriptors of the geometry of supercoiled DNA molecules: linking, twisting, and writhing. These quantities are related by a fundamental theorem with important consequences for experimental biology, because it allows biologists to infer any one of the quantities from measurements of the other two. Deoxyribonucleic acid (DNA) is usually envisioned as a pair of helices, the sugar-phosphate backbones, winding around a common linear axis. In the famous model of Crick and Watson, one turn of the double helix occurs approximately every 10.5 base pairs. However, the actual structure of DNA in a cell is typically more complex: the axis of the double helix may itself be a helix or may, in general, assume almost any configuration in space. In the late 1960s it was discovered that many DNA molecules are also closed; that is, the axis as well as the two backbone strands are closed curves. (A closed curve is a curve of finite length, the "starting point" and "endpoint" of which coincide.) In this case the DNA is called closed circular or simply closed. This chapter is

WINDING THE DOUBLE HELIX: USING GEOMETRY, TOPOLOGY, AND MECHANICS OF DNA 154 concerned with the geometry, topology, and energetics of closed supercoiled DNA. Supercoiling of closed DNA is ubiquitous in biological systems. It can arise in two ways. First, it can result when DNA winds around proteins. Second, supercoiling can also result from topological constraints known as under- or overwinding, in which case the axis of the DNA usually assumes an interwound, or plectonemic, form. Supercoiling is important for a wide variety of biological processes. For example, supercoiling is a way of storing free energy—which can be used to assist the vital processes of replication and transcription, processes that require untwisting or separation of DNA duplex strands. Thus, supercoiling helps enzymes called helicases, polymerases, and other proteins to force apart the two strands of the DNA double helix, allowing access to the genetic information stored in the base sequence. It also promotes a variety of structural alterations that lead to DNA unwinding, such as z-DNA (left-handed double helical DNA) and cruciforms (cross-shapes). In higher organisms, supercoiling helps in cellular packaging of DNA in structures called nucleosomes, in which DNA is wound around proteins called histones. It is crucial in bringing together and aligning DNA sequences in site-specific recombination. It also changes the helical periodicity (number of base pairs per turn) of the DNA double helix; such changes can alter the binding of proteins to the DNA or the phasing of recombinant sequences. Understanding supercoiled DNA is thus essential for the understanding of these diverse processes. Numerous biological experiments—including those based on sedimentation, gel electrophoresis, electron microscopy, X-ray diffraction, nuclease digestion, and footprinting—can give information about these matters. However, mathematical methods for describing and understanding closed circular DNA are needed to explain and classify the data obtained from these experiments. This chapter defines and elucidates the major geometric descriptors of supercoiled DNA: linking, twisting, and writhing. It applies these concepts to classify the action of the major types of cutting enzymes, topoisomerases of Type I and Type II. It then develops the differential topological invariants necessary to describe the structural changes that occur in the DNA that is bound to proteins. Other chapters in this book explore applications of topology and geometry to DNA coiling. Chapter 7

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As researchers have pursued biology's secrets to the molecular level, mathematical and computer sciences have played an increasingly important role—in genome mapping, population genetics, and even the controversial search for "Eve," hypothetical mother of the human race.

In this first-ever survey of the partnership between the two fields, leading experts look at how mathematical research and methods have made possible important discoveries in biology.

The volume explores how differential geometry, topology, and differential mechanics have allowed researchers to "wind" and "unwind" DNA's double helix to understand the phenomenon of supercoiling. It explains how mathematical tools are revealing the workings of enzymes and proteins. And it describes how mathematicians are detecting echoes from the origin of life by applying stochastic and statistical theory to the study of DNA sequences.

This informative and motivational book will be of interest to researchers, research administrators, and educators and students in mathematics, computer sciences, and biology.

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