The Watson-Crick double helix is perhaps the most predictable and programmable of all intermolecular interactions. In addition to its biological role in the cell, double helical DNA is used for DNA-based computation and for DNA nanotechnology. The success of these applications has been based on the reliability of Watson-Crick base pairing, and, in the latter case, circumventing the linearity of the double helix. We survey some of the alternative base pairing structures that can be found in synthetic systems, indicating motifs that can be propagated and giving examples of mispairing that can occur within the double helical context. We discuss some of the more common covalent modifications of nucleic acids. We also indicate the structural interplay of special sequences and negative supercoiling. In addition to the caveats that we present involving unexpected results in nucleic acid systems, we show that the process of reciprocal exchange and the generalization of complementarity can be used to generate branched DNA motifs for use in DNA nanotechnology or DNA-based computation. We show that these motifs can be used for the directed construction of DNA objects, for the generation of specific designed patterns in two-dimensional lattices, for computation by self-assembly, and for the fabrication of DNA-based nanodevices. The use of non-Watson-Crick DNA leads inherently both to errors and to thrilling possibilities. Successfully juggling these aspects of generalized nucleic acid structure is an exciting challenge to investigators in the area.
['Nadrian C. Seeman']
It started with Watson and Crick, but it sure didn't end there: Pitfalls and possibilities beyond the classic double helix