DNA architecture: from G to Z

Abstract

G-quadruplexes and Z-DNA are two important non-B forms of DNA architecture. Results on novel structural elements, folding and unfolding kinetics, and interactions with small molecules and proteins have been reported recently for these forms. These results will enhance our understanding of the biology of these structures and provide a platform for drug design.

Figure 1

Polymorphism of the loops connecting individual strands of the G-quadruplex: (a) edgewise loop, (b) diagonal loop, (c) double-chain-reversal loop and (d) V-shaped loop. Adapted with permission from [69].

Figure 2

Telomeric G-quadruplexes. (a,b) Structures formed by the human telomeric sequence d[AGGG(TTAGGG)₃] (a) in Na⁺ solution [5] and (b) in K⁺ crystal [6]. (c,d) Structures formed by the human telomeric sequence d(TAGGGTTAGGGT) in K⁺ solution [7^••]: (c) parallel form and (d) antiparallel form. (e,f) Structures formed by the Tetrahymena telomeric sequence d(TGGGGTTGGGGT) in Na⁺ solution [15]: (e) head-to-head form and (f) head-to-tail form. Loops are colored red; anti and syn guanines are colored cyan and magenta, respectively.

Figure 3

G-quadruplex topologies containing the (3+1) G-tetrad core. (a) (3+1) G-quadruplex formed through dimerization of a three-repeat human telomeric sequence [16^••]. (b) Intramolecular G-quadruplex formed by the Tetrahymena d(T₂G₄)₄ sequence [17]. Color coded as in Figure 2.

Figure 4

Novel structural elements in G-quadruplexes. (a) Fold-back G-quadruplex of the five-G-tract c-myc promoter sequence [23^••], (b) interlocked dimeric G-quadruplex of 93del [24^••], (c) i-motif of G-quartets [27] and (d) dimeric G-quadruplex of d(GGGTTTTGGGG) [28^•]. Color coded as in Figure 2.

Figure 5

Interaction of G-quadruplexes with small molecules, as reported by (a) Clark et al. [39^•] for the parallel quadruplex–daunomycin complex, (b) Gavathiotis et al. [40] for the parallel G-quadruplex bound to two molecules of a fluorinated polycyclic methyl-acridinium salt, (c) Phan et al. [23^••] for the G-quadruplex–TMPyP4 complex and (d) Haider et al. [41^••] for the complex between an antiparallel G-quadruplex and a disubstituted aminoalkylamido acridine. Guanine bases are colored cyan, O4′ are colored yellow and ligands are colored magenta.

Figure 6

Structure of the B-Z DNA junction [62^••]. Views highlighting (a) flipped-out bases of the junctional pair, (b) opposing minor grooves flanking looped-out bases of the junctional pair, and (c) stacking arrangement of base faces at junctional and flanking sites.

Figure 7

Recognition of a three-way DNA junction by a metallosupramolecular helicate. (a) [Fe₂L₃]⁴⁺ (L = C₂₅H₂₀N₄) tetracationic supramolecular helicate, with the Fe²⁺ ions represented as red spheres. (b) Structure of a three-way DNA junction bound to [Fe₂L₃]⁴⁺. Three DNA strands are colored cyan, magenta and gray, respectively.