An intramolecular quadruplex of (GGA)(4) triplet repeat DNA with a G : G :G : G tetrad and a G(: A): G(: A): G(: A): G heptad, and its dimeric interaction

The structure of d(GGAGGAGGAGGA) containing four tandem repeats of a GGA tr iplet sequence has been determined under physiological K+ conditions. d(GGA GGAGGAGGA) folds into an intramolecular quadruplex composed of a G:G:G:G te trad and a G(:A):G(:A):G(:A):G heptad. Four G-G segments of d(GGAGGAGGAGGA) are aligned parallel with each other due to six successive turns of the ma in chain at each of the GGA and GAGG segments. Two quadruplexes form a dime r stabilized through a stacking interaction between the heptads of the two quadruplexes. Comparison of the structure of d(GGAGGAGGAGGA) with the repor ted structure of d(GGAGGAN) (N = G or T) containing two tandem repeats of t he GGA triplet revealed that although the two structures resemble each othe r to some extent, the extension of the repeats of the GGA triplet leads to distinct structural differences: intramolecular quadruplex for 12-mer versu s intermolecular quadruplex for 7-mer; heptad versus hexad in the quadruple x; and three sheared G:A base-pairs versus two sheared G:A base-pairs plus one A:A base-pair per quadruplex. It was also suggested that d(GGAGGAGGAGGA ) forms a similar quadruplex under low salt concentration conditions. This is in contrast to the case of d(GGAGGAN) (N = G or T), which forms a duplex under low salt concentration conditions. On the basis of these results, th e structure of naturally occurring GGA triplet repeat DNA is discussed.