FUNDAMENTALS OF DNA AND RNA STRUCTURE
In 1946, Avery provided concrete experimental evidence that DNA was the main constituent of genes (Avery et al., 1944); universal acceptance of this idea came with the publication of the Hershey-Chase experiments (Hershey and Chase, 1951). After the seminal discovery of the double helical nature of DNA in 1953 (Watson and Crick, 1953), the focus of nucleic acid structural research turned to fiber diffraction of natural and defined sequences (Arnott 1970; Arnott, Campbell Smith, and Chandrasekaran, 1976a). Through these studies, we gained many insights into nucleic acid structure. We learned that hydration, ionic strength, and sequence affect conformation type and that nucleic acids can adopt a wide variety of structures including single-stranded helices (Arnott, Chandrasekaran, and Leslie, 1976b) and parallel helices (Rich et al., 1961), as well as triple and quadruple helices (Arnott, Chandrasekharan, and Marttila, 1974).
Once it was possible to synthesize and purify oligonucleotides (Khorana et al., 1956), crystallography and later NMR could be used to determine nucleic acid structures. The first crystal structure that was identified as containing all the components that could have allowed us to see a double helix was a very small piece of RNA—the dinucleoside monophosphate Up Å (Seeman et al., 1971). But rather than forming a double helix, it displayed unusual conformations, ...