molecules.^29 But while ions are often visible in structures of nucleic acids, it is not straightforward to
determine how they affect the structure. The question of whether cations can assume specific roles in the
control of DNA duplex conformation has stirred up controversy in recent years. Some in the field, notably
Nicholas Hud and Loren Williams, believe that cation localisation within the grooves of DNA represents
a significant factor in sequence-specific helical structure. By contrast, probably a majority of those study-
ing the structure of DNA is of the opinion that the specific sequence dictates local DNA conformation and
thus binding of metal cations. According to this second view, metal ions can bind to DNA in a sequence-
specific manner and in turn modulate the local structure, but ions should not be considered the single most
significant driving force of a number of DNA conformational phenomena.
To study the possible effects of metal ions on DNA conformation, all sequences can be divided into
three principal groups: A-tracts, G-tractsand generic DNA, the latter representing the vast majority of DNA
sequences.^30 A-tracts have an unusually narrow minor groove, are straight and have high base pair pro-
peller twist (see also Figures 2.18 and 2.19). G-tracts have a propensity to undergo the B-form→A-form
transition at increased ionic strength. The proponents of the ‘ions are dominant’model believe that the DNA
grooves are flexible ionophores and that DNA duplex structure is modulated by a tug of war between the
two grooves for cation localisation. They argue that the duplex geometry adopted by A-tracts (referred to
as B*-DNA, Figure 2.28a) is due to ion localisation in the minor groove as a result of the highly negative
electrostatic potentials there. Conversely, G-tract DNA exhibits a highly negative electrostatic potential in the
major groove (Figure 2.28b), leading to preferred localisation of cations there and consequently a collapse
of the DNA around the ions. Generic DNA on the other hand would have a more balanced occupation of
DNA and RNA Structure 43
Figure 2.27 The Holliday junction adopted by four DNA decamers with sequence TCGGTACCGA (PDB: 1M6G).
The view illustrates the side-by-side arrangement of the two duplex portions, with the A nucleotides (red) C
nucleotides (pink) of two decamers that form the core of the junction visible near the centre. The positions
of phosphate groups in the backbones of individual oligonucleotides are traced with ribbons