However, it is becoming clear that although the general structure of DNA is important in the overall mechanism of replication ( Watson & Crick, 1953a), the conformational details are important for understanding how proteins recognize their cognate DNA sequence, and how mutations may be introduced and are repaired. One would think that, for replication, we need only be concerned with the DNA duplex at the beginning, the single-stranded intermediate state, and the final duplex, since these structures generally tell us how the information is stored and read, and what the resulting product is. Replication is the process by which the cell creates an exact copy of the genetic information encoded in DNA-it is thus intuitive that we would be interested in the actual structure of DNA as a molecule. Although B-DNA is the standard form in the cell, we suggest that this dance away from the norm is essential for cellular function, giving the cell life and, hence, its genetic soul. We will explore the conformational variations that lead from double-helices to complexes composed of three or four strands, then consider how conformations interconvert through various intermediates.

We start our journey by presenting the fundamental principles that serve as the vocabulary to analyze and describe the features of nucleic acid structures. In this chapter, we dive into the cellular pot and find a literal alphabet soup of DNA structures. A deeper appreciation for how DNA functions comes from the recognition that this is a highly malleable molecule, providing the cell with a plethora of conformations to exploit in replication and transcription.Some of these conformations can give rise to mistakes, while others help to repair those mistakes in the genetic code. For many biologists, this simple, but elegant structure is all that is needed for a basic, albeit superficial understanding of cellular genetics. The story of DNA structure is as varied as it is interesting, the most famous tale being the “discovery” of B-DNA by Watson and Crick.

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