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Suggested Citation:"REFERENCES." 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 200
Suggested Citation:"REFERENCES." 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 201

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UNWINDING THE DOUBLE HELIX: USING DIFFERENTIAL MECHANICS TO PROBE CONFORMATIONAL CHANGES IN 200 DNA signal sequences, several of which are very close together, including both known poly-adenylation sites. As a second example, a search of all known E. coli sequences finds more than 100 locations having the sequence associated with LexA binding. Analysis of which of these sites are destabilized could suggest whether some might be promoters for previously unrecognized SOSregulated genes. The transition behavior of stressed DNA molecules can be complicated by several additional factors. First, there are other types of transitions possible for specific sequences within a DNA molecule. For example, sequences in which a purine (A or G) alternates with a pyrimidine (C or T) along each strand can adopt a left- handed helical structure. Transitions to this and to other alternative conformations also can be driven by imposed superhelicity. So the equilibrium experienced by a stressed molecule actually involves competition among several types of transitions, not just strand separation. Because these other conformations usually are possible only at a small number of short sites having the correct sequence, their analysis is combinatorially simpler than the treatment of strand separation. The theoretical methods described here are currently being extended to include the possible occurrence of other types of transitions. The second complication arises from the structural restraints on DNA in cells. There the DNA is not free to twist and writhe to minimize its energy, but instead is wound around basic proteins to form a chromatin fiber. This drastically alters the types of deformations the molecule can undergo. While it is not clear precisely how this constraint interacts with superhelicity, conformational transitions are expected to be driven by less extreme deformations in restrained molecules than in unrestrained ones (Benham, 1987). The approach outlined here has great promise for finding biologically important correlates of regulation and for illuminating specific mechanisms of function. REFERENCES Benham, C.J., 1987, ''The influence of tertiary structural restraints on conformational transitions in superhelical DNA," Nucleic Acids Res. 15, 9985-9995. Benham, C.J., 1990, "Theoretical analysis of heteropolymeric transitions in superhelical DNA molecules of specified sequence," J. Chem. Phys. 92, 6294-6305.

UNWINDING THE DOUBLE HELIX: USING DIFFERENTIAL MECHANICS TO PROBE CONFORMATIONAL CHANGES IN 201 DNA Benham, C.J., 1992, "Energetics of the strand separation transition in superhelical DNA," Journal of Molecular Biology 225, 835-847. Benham, C.J., 1993, "Sites of predicted stress-induced DNA duplex destabilization occur preferentially at regulatory loci," Proceedings of the National Academy of Sciences USA 90, 2999-3003. Bhriain, N. Ni, C. Dorman, and C. Higgins, 1989, "An overlap between osmotic and anaerobic stress responses: A potential role for DNA supercoiling in the coordinate regulation of gene expression," Mol. Microbiol. 3, 933-942. Dorman, C., G. Barr, N. Ni Bhriain, and C.F. Higgins, 1988, "DNA supercoiling and the anaerobic and growth phase regulation of tonB gene expression," J. Bacteriol. 170, 2816-2826. Gellert, M., 1981, "DNA topoisomerases," Annu. Rev. Biochem. 50, 879-910. Hartwig, M., E. Matthes, and W. Arnold, 1981, "Extremely underwound chromosomal DNA in nucleoids of mouse sarcoma cells," Cancer Letters 13, 153-158. Kowalski, D., and M. Eddy, 1989, "The DNA unwinding element: A novel cis-acting component that facilitates opening of the Escherichia coli replication origin," EMBOJ. 8, 4335-4344. Kowalski, D., D. Natale, and M. Eddy, 1988, "Stable DNA unwinding, not breathing, accounts for single-strand specific nuclease hypersensitivity of specific A+T−rich regions," Proceedings of the National Academy of Sciences USA 85, 9464-9468. Malkhosyan, S., Y. Panchenko, and A. Rekesh, 1991, "A physiological role for DNA supercoiling in the anaerobic regulation of colicin gene expression," Mol. Gen. Genet. 225, 342-345. Marmur, J., and P. Doty, 1962, "Determination of the base composition of deoxyribonucleic acid from its thermal denaturation temperature," Journal of Molecular Biology 5, 109-118. Mattern, M., and R. Painter, 1979, "Dependence of mammalian DNA replication on DNA supercoiling," Biochim. Biophys. Acta 563, 293-305. Pruss, G., and K. Drlica, 1989, "DNA supercoiling and prokaryotic transcription," Cell 56, 521-523. Schildkraut, C., and S. Lifson, 1968, "Dependence of the melting temperature of DNA on salt concentration," Biopolymers 3, 195-208. Smith, G., 1981, "DNA supercoiling: Another level for regulating gene expression," Cell 24, 599-600. Umek, R., M. Linskens, D. Kowalski, and J. Huberman, 1989, "New beginnings in studies of eucaryotic DNA replication origins," Biochem. Biophys. Acta 1007, 1-14. Weintraub, H., P. Cheng, and K. Conrad, 1986, "Expression of transfected DNA depends on DNA topology," Cell 46, 115-122. White, J.H., 1988, "An introduction to the geometry and topology of DNA structure," pp. 225-254 in Mathematical Methods for DNA Sequences, M.S. Waterman (ed.), Boca Raton, Fla.: CRC Press. Wu, H., S. Shyy, J.C. Wang, and L.F. Liu, 1988, "Transcription generates positively and negatively supercoiled domains in the template," Cell 53, 433-440.

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Calculating the Secrets of Life: Contributions of the Mathematical Sciences to Molecular Biology Get This Book
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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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