Left-Handed DNA in Chemical and Biological Systems

Abstract

DNA can have both right-handed and left-handed double helical conformations. This idea has old roots and was considered shortly after the formulation of the double helix by Watson and Crick in 1953 (1). In this early period, attention was directed toward the question of whether or not the X-ray diffraction patterns of DNA fibers were consistent with the Watson and Crick formulation. Efforts spanning over a decade produced a great deal of experimental evidence which in essence stated that it was possible to modify the initial Watson-Crick right-handed helix in a number of details so that one could produce a model consistent with the experimental X-ray data (2). It was obvious to workers in the field, however, that although DNA fiber analysis generated physical data in agreement with the Watson-Crick structure, they did not unambiguously prove the structure. The X-ray diffraction patterns were limited, and far from atomic resolution. Because of the limited resolution the patterns had to be interpreted and a number of assumptions made. One assumption was that the structure was perfectly regular with an asymmetric unit consisting of one nucleotide. However, the agreement was reasonable and this led to the general adoption of the right-handed B-DNA conformation as the predominant form in biological systems. Considerable attention was paid to the fact that under certain conditions alternative conformational variants were seen. The most important of these was the A-DNA pattern which originally was produced by air-dried fibers (3). The greater wealth of diffraction data seen in the A pattern made it possible to get more information. The relative ease with which it slipped into the B pattern reinforced the idea that these were two conformational variants; it was found that both patterns could be fitted by a right-handed double helix.