Nucleic acids and chromatin
Nucleic acids and chromatin

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Nucleic acids and chromatin

Triplex structures

An unusual form of three-stranded structure, called triplex DNA, can arise in vitro when a single-stranded region of DNA pairs with a paired duplex DNA helix through additional hydrogen bonding between the bases of all three strands.

SAQ 18

Based upon your knowledge of the structure of helical DNA, where would you predict that a short DNA strand would ‘sit’ within this structure for such an interaction to occur?

Answer

Within the major groove, where several potential hydrogen bonding sites are available, as shown in Figure 9c.

The formation of these hydrogen bonds arises because of what are termed Hoogsteen bonds, which form between bases in the incoming single-stranded DNA and the already paired bases in the duplex, as shown in Figure 15. The various combinations of bonds, C–G·C, T–A·T, T–A·A and C–G·G (where the dash denotes Watson-Crick base pairing and the dot denotes Hoogsteen pairing), have varying degrees of stability, with bonds between the purines being most stable. Whilst many in vitro studies have examined the possible structures of these triplex DNAs, their role in vivo remains unclear. Their significance lies in the observation that triplex structures in vitro have been shown to inhibit transcription. Thus formation of these structures in vivo, for example between a duplex region and single-stranded DNAs or between two duplex regions (as shown in Figure 15b), could play a role in gene regulation.

Figure 15
Figure 15 Triplex DNA and Hoogsteen pairs. (a) Triplex DNA secondary structure formed between a 14 base-pair helical duplex (shown as tubes) and a six-base single-stranded DNA (space-filling) lying within the major groove (pdb file 1bwg). (b) Possible interactions between duplex DNA and either single-stranded DNA or a second duplex DNA. (c) Molecular details of the Hoogsteen bonds to the Watson-Crick base pairs, resulting in four base triplet combinations (dR = deoxyribose). Notice that the formation of the C–G·C triplet requires a protonation of the cytosine base in the single-stranded DNA.
S377_1

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