Abstract

In nature and in the test tube, nucleic acids occur in many different forms. Apart from single-stranded, coiled molecules, DNA and RNA prefer to form helical arrangements, in which the bases are stacked to shield their hydrophobic surfaces and expose their polar edges. Focusing on double helices, we describe the crucial role played by symmetry in shaping DNA and RNA structure. The base pairs in nucleic-acid double helices display rotational pseudo-symmetry. In the Watson–Crick base pairs found in naturally occurring DNA and RNA duplexes, the symmetry axis lies in the base-pair plane, giving rise to two different helical grooves. In contrast, anti-Watson–Crick base pairs have a dyad axis perpendicular to the base-pair plane and identical grooves. In combination with the base-pair symmetry, the syn/anti conformation of paired nucleotides determines the parallel or antiparallel strand orientation of double helices. DNA and RNA duplexes in nature are exclusively antiparallel. Watson–Crick base-paired DNA or RNA helices display either right-handed or left-handed helical (pseudo-) symmetry. Genomic DNA is usually in the right-handed B-form, and RNA double helices adopt the right-handed A-conformation. Finally, there is a higher level of helical symmetry in superhelical DNA in which B-form double strands are intertwined in a right- or left-handed sense.

Highlights

  • Nucleic acids are inherently asymmetric molecules, yet in their biologically prevalent, base-paired and helical forms, DNA and RNA display several levels of symmetry

  • There is a higher level of helical symmetry in superhelical DNA in which B-form double strands are intertwined in a right- or left-handed sense

  • To conclude the discussion of DNA and RNA helix types as revealed by X-ray fiber diffraction studies, we may state that the canonical A, B- and Z-forms are clearly distinct, as they differ in their helical symmetry and several other structural features (Table 2)

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Summary

Introduction

Nucleic acids are inherently asymmetric molecules, yet in their biologically prevalent, base-paired and helical forms, DNA and RNA display several levels of symmetry. Their constituents, nucleobases, nucleosides and nucleotides, do not have any non-trivial symmetry. A well-known example of this concept, for which we will use the term “pseudo-symmetry” below, are the Watson–Crick base pairs of double-stranded DNA and RNA, which have similar shapes and whose dyad symmetry axes superimpose their glycosyl bonds after rotation. We focus on symmetry properties of double-stranded DNA and RNA, an aspect of these structures that has not received much attention so far, and illustrate them with examples from the published literature. Our selection of specific examples is slightly biased towards our own work; we apologize to all authors whose work could not be cited out of considerations of economy and readability

Symmetry of Base Pairs
Symmetry of Nucleoside Pairs
Guanine
The A-Form of RNA and DNA
Canonical
B-Like Forms of DNA
The Z-Form of DNA
Double Helix Structure Modulation by Mis-Pairing and Chemical Modification
Double Helix Structure Modulation by Ligand Binding
The Biology of Double-Helical DNA Structures
Conclusions
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