Folding Topology of a Bimolecular DNA Quadruplex Containing a Stable Mini-hairpin Motif within the Diagonal Loop

A single base permutation in any loop of a folded intramolecular quadruplex influences its structure and stability

“…It is well established that the folding motif for any DNA intramolecular quadruplex is highly regulated by the types of loops present [15][16][17][18][19][20]. The types of loops present will determine: 1) the syn or anti conformations of the guanine bases; 2) the strand orientations (i.e., parallel, antiparallel or mixed parallel-antiparallel); and 3) the orientation of the hydrogen bonds within one G-tetrad relative to the G-tetrad above and below [21].…”

Structural Basis of DNA Quadruplex–Duplex Junction Formation

“…We first demonstrated that a duplex can be extended seamlessly across the wide groove of an antiparallel Gquadruplex [16] (construct I, "JWC": junction across wide groove with two continuous strands; Figure 2 a, Table S2 and Figure S2 in the Supporting Information). There is a gradual transition between the minor groove of the duplex and the wide groove of the quadruplex (strand separation expanding from 18 to 19 ), and this compatibility was shown to apply universally across wide grooves of different Gquadruplexes ( Figure S3 in the Supporting Information). Continual stacking of bases over the duplex and quadruplex segments contributes towards the overall stability of the structure.…”

“…To connect a duplex across the diagonal corners [18,19] of a tetrad (the phosphate groups would have to span a distance of > 20 ), an adaptor G·A Watson-Crick mismatch base pair [20] could be placed at the junction to ease the transition between the two segments with different dimensions (construct III, "JDC": junction across diagonal corners with two continuous strands; Figure 2 c, Table S4 and Figure S6 in the Supporting Information). There is an associated displacement of the helical axis of the duplex with respect to that of the quadruplex.…”

“…Note that even though the sequences were arbitrarily conceived, the five quadruplex-duplex constructs (Figure 2) were designed to cover the fundamental aspects of the connectivity between a duplex and a quadruplex (or the incorporation of a duplex in a quadruplex loop). [19,25,26] Junction variants can be rationalized as an adaptation or composite of the junctions presented. However, we should not discard the possibility that more exotic junction types may yet exist.…”

The many twists and turns of DNA: template, telomere, tool, and target

“…Overall, these findings provide further support for the heterogeneity of strand topology and loop conformation in G-quadruplexes. Loops of different orientation were also observed in structures of bimolecular antiparallel DNA quadruplexes [d(G 3 ACGTAGTG 3 )] 2 and [d(G 3 T 4 G 3 )] 2 , whereby the former contains an autonomously stable mini-hairpin motif inserted within the diagonal loop [21] (2kaz). Thus, the nature of the loop sequence and the formation of interactions between loops and the G-quadruplex core are important elements in controlling quadruplex topology and stability.…”