Triple-stranded DNA

A triple-stranded DNA is a structure of DNA in which three oligonucleotides wind around each other and form a triple helix. In this structure, one strand binds to a B-form DNA double helix through Hoogsteen or reversed Hoogsteen hydrogen bonds.

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For example, a nucleobase T binds to a Watson-Crick base-pairing of T-A by Hoogsteen hydrogen bonds between an AxT pair (x represents a Hoogsteen base pair). An N-3 protonated cytosine, represented as C+, can also form a base-triplet with a C-G pair through the Hoogsteen base-pairing of an AxC+. Thus, the triple-helical DNAs using these Hoogsteen pairings consist of two homopyrimidines and one homopurine, and the homopyrimidine third strand is parallel to the homopurine strand.

A homopurine third strand can also bind to a homopurine-homopyrimidine duplex using reversed Hoogsteen patterns. In this triplex, a nucleobase A binds to a T-A base pair and a G to a C-G pair. Since the nucleobases on the third strand have to be reversed, the homopurine third strand is antiparallel to the homopurine strand of the original duplex.

Triple-stranded DNA was first described in 1957. It is known to occur in only one in vivo biological process: as an intermediate product during the action of the E. coli recombination enzyme RecA. Its role in that process is not understood.

Using nucleic acid segments that bind to the DNA duplexes to form triple strands as a way of regulating gene expression is under investigation by biotechnology companies. Similar work is also being undertaken at Yale University.

References

• Rich, A. (1993). DNA comes in many forms. Gene 135:99-109
• Mills, M., Arimondo, P., Lacroix, L., Garestier, T., Hélène, C., Klump, H. & Mergny, J.L. (1999). Energetics of strand displacement reactions in triple helices: a spectroscopic study. J. Mol. Biol. Vol. 291: 1035-1054