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.
Prof. Nadrian
C. Seeman
Department of Chemistry
New York University
New York, NY 10003, USA
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