Workshop on DNA Sequence and Topology

Dates: April 19 - 20, 2001
DIMACS Center, Rutgers University, Piscataway, NJ

Wilma K. Olson, Rutgers University,
Bernard D. Coleman, Rutgers University,
Victor B. Zhurkin, NIH,
Presented under the auspices of both the DIMACS Special Focus on Computational Molecular Biology and The Center for Molecular Biophysics and Biophysical Chemistry at Rutgers University, and with support from PMMB (The Program on Mathematics and Molecular Biology based at Florida State University).

The packaging of DNA within the close confines of the cell imposes a higher order structure on the long threadlike molecule. The chain must fold and adopt arrangements that allow for correct recognition and processing of the genetic message. This organizational structure is only beginning to be understood. We know, for example, that the linear sequence of genetic information also includes a base sequence-dependent spatial and energetic code that governs the global folding of the double helix and its susceptibility to interactions with other molecules (Olson et al., 1998) and that basic biological processes, such as the transcription of the genetic code, the replication of DNA, and the repair of damaged DNA, are based on mechanisms sensitive to these physical properties (Peter et al., 1998).

Access to the genetic code requires severe changes in local DNA structure. Proteins usually gain access to the atoms holding the code by a partial unwinding and bending of the double helix, processes that can give rise in the DNA to ``supercoiling'' (Bauer et al., 1980). Deciphering the sequence-dependent structural and deformational codes in DNA as well as the interplay between the local and long-range structure associated with its biological activity require a variety of mathematical and computational approaches: tools to extract knowledge-based ``energies'' from structural and thermodynamic nucleic acid databases, such as those organized at Rutgers (Berman et al., 1992); techniques to simulate the dynamical structures and equilibrium properties of ensembles of DNA molecules, (Beveridge, 1998; Jian et al., 1998); explicit and exact solutions of the non-linear equations governing the supercoiled shapes of a deformable DNA elastic rod (Goldstein et al., 1998; Swigon et al., 1998); analysis of the topological forms of DNA produced by enzymatic action (Crisona et al., 1999); explicit expressions to incorporate base sequence-dependent structural information in genomic analyses, (Sheridan et al., 1998; Yeramian, 1999).

This workshop will bring together such diverse perspectives on DNA topology to build bridges not only between mathematics and molecular biology but also between the mathematical and physical scientists currently focused on either the local or global view of DNA structure. This workshop follows two previous DIMACS workshops on DNA topology. Those dealt exclusively with the global folding of idealized, sequence-independent DNA rods and made no connection to the structural and energetic information embedded in the genetic code. The databases of DNA 3D structures have grown to the point where only now is it possible to extract the sequence-dependent information required to connect macromolecular structure and properties to the sequence of DNA base pairs, making this workshop extremely timely.


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Crisona, N.J., Weinberg, R.L., Peter, B.J., Sumners, D.W. & Cozzarelli, N.R.
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Goldstein, R.E., Powers, T.R. & Wiggins, C.H. (1998). Viscous nonlinear
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mononucleosomes. Biophys. J. 74, 2515-2530.

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Document last modified on January 11, 2001.