Three-stranded triplex DNA occurs when single-stranded DNA forms Hoogsteen
hydrogen bonds in the major groove of purine-rich double-stranded B-DNA142 (see the
figure, part c). Triplexes in which the third strand is antiparallel to the DNA duplex can
form at physiological pH, and these structures are stabilized by negative supercoiling142 Sequences capable of forming triplexes are common in eukaryotes but much rarer in
prokaryotes143. In mammals, triplex-forming motifs are enriched in the introns of a
variety of essential genes, including those involved in development and signalling144.
Additionally, triplexes are hypothesized to cause genomic instability by causing doublestrand
breaks that result in translocations145. However, the formation of a triplex
structure in a trinucleotide repeat sequence (for example, (CAG)n) can prevent the
expansion of the repeat138,139; repeat expansion is related to human genetic
disorders146,147.