G- and C-rich strands are found at the telomeric ends of chromosomes (see Section 6.4.5), and such
sequences are of fundamental importance in protecting the cell from re-combination and degradation. It is
known that when DNA containing a palindromic sequence of bases is subjected to supercoiling stress
(Section 2.3.5), a cruciform can be extruded (Figure 2.26). If the tips of the cruciform extrusions contain
C residues in one limb and G residues in the other, G- and C-rich quadruplexes can be formed by com-
bining two cruciforms of this type. So it is possible that formation of four-stranded G- and C-rich motifs
provides the physical basis for identical DNA sequences to bind together, i.e.during meiosis when identi-
cal chromosomes line up with each other. Proteins that bind to G-rich quadruplexes have been identified
and it is unlikely that the C-rich motif is stable at neutral pH without also binding a protein factor, since
the motif is held together by hemiprotonated CCbase pairs.
The structures of G- and C-rich quadruplexes are fundamentally different. In the case of four-stranded
G-rich motifs, guanines join together via cyclic hydrogen bonding that involves four guanines at each level
(often called a G-tetrador G-quartet) (Figure 2.35). Each G base is engaged in four hydrogen bonds via its
Hoogsteen and Watson–Crick faces, such that guanines are related by a four-fold rotation axis and are nearly
co-planar. In this way, each guanine directs its O-6 carbonyl oxygen into the central core of the tetrad.
Although it had been found as early as 1910 that concentrated solutions of guanylic acid were unusually
viscous and formed a clear gel upon cooling (see Section 1.3) and Gellert and Davies had described a four-
stranded helix for guanylic acid based on fibre diffraction experiments more than 40 years ago, detailed 3D
DNA and RNA Structure 53
Figure 2.35 (a) The parallel-stranded G-tetrad motif formed by two molecules d(TAGGGTTAGGGT) (PDB: 1K8P).
The directions of the sugar–phosphate backbones are traced by ribbons. The view is from the side,
illustrating the disc-like shape with the three G-tetrad layers on the inside and the TTA ‘propellers’
on the outside. The 5-termini of both strands are pointing downwards. (b) Schematic line diagram
illustrating the relative orientation of the two strands and the formation of three layers of G-quartets