Our laboratory is investigating unusual DNA molecules in model systems that use synthetic molecules. A major effort in our laboratory is devoted to DNA Nanotechnology.The attachment of specific sticky ends to a DNA branched junction enables the construction of stick figures, whose edges are double-stranded DNA. This approach has already been used to assemble a cube, a truncated octahedron , nanomechanical devices and 2-D crystals and 3-D crystals from DNA. Ultimate goals for this approach include the assembly of a biochip computer, nanorobotics and nanofabrication and the exploitation of the rational synthesis of periodic matter. This methodology also has applications to DNA Based Computing.
Our interest in branched DNA was originally stimulated by a desire to characterize Holliday junctions. These are four-arm branched DNA molecules that are found to be structural intermediates in genetic recombination. The focus of the work on these unusual molecules is to characterize the biophysics of recombination intermediates, particularly their structure, dynamics and thermodynamics, and to establish the relationship between these properties and their biological function. In the last few years, the symmetry, crossover topology and sequence-dependent thermodynamics of the 4-arm junction have been characterized and analyzed. The study of recombination intermediates has been extended by constructing and analyzing molecules with double crossovers, and by exploring broader classes of multi-stranded molecules, called antijunctions and mesojunctions. Recently, we have used Bowtie junctions to examine the properties of Holliday junctions.
Knotted DNA molecules have also been constructed, because they are recombination intermediate analogs, because they offer a window on stressed DNA, and because they may permit us to clone the complex catenanes that we make in our DNA nanotechnology program. The program on single-stranded Nucleic Acid Topology has led to characterization of the interactions of synthetic DNA knots with topoisomerases, to a general algorithm for the construction of any DNA knot, to the synthesis of a DNA molecule that can be built to yield four different topological species , to the discovery of an RNA topoisomerase, and to the construction of Borromean Rings.
The physical techniques used in the laboratory include X-ray crystallography, computer graphics-aided molecular modeling and design, AFM, FRET, gel electrophoresis and automated oligonucleotide synthesis. Our published work in these areas is summarized in the Structural Studies Bibliography.
Ned Seeman's biographical highlights.
Department of Chemistry
New York University
New York, NY 10003, USA
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