The triple-stranded DNA structure found in homopurine–homopyrimidine regions is called H-DNA. It is an unusual intramolecular DNA triplex in which part of a duplex folds back so that a third strand binds in the major groove.
H-DNA forms in sequences rich in purines on one strand and pyrimidines on the other, especially when the DNA is negatively supercoiled. The folded-back third strand uses Hoogsteen or reverse-Hoogsteen hydrogen bonding rather than relying solely on the familiar Watson–Crick pairing of the original double helix. Common base triplets include T-A*T and C-G*A+.
The structure is sensitive to chemical conditions. Classical H-DNA is favored by acidic conditions because cytosine must often be protonated, and divalent ions such as magnesium can help stabilize the triplex. A related form, H*-DNA, uses a different strand orientation and can be more favorable near neutral pH.
H-DNA is not the same as a G-quadruplex, which is built from stacked guanine tetrads, or an R-loop, which contains an RNA–DNA hybrid and a displaced DNA strand. Triplex DNA was proposed in the 1950s, and later work showed that homopurine–homopyrimidine mirror repeats in supercoiled DNA can adopt this alternative structure.