It is emerging that DNA tetraplexes are pivotal for many major cellular pro
cesses, and techniques that assess their structure and nature to the point
are under development. Here we show how the structural conversion of largel
y unstructured single-stranded DNA molecules into compact intrastrand DNA t
etraplexes can be monitored by fluorescence resonance energy transfer.
We recently reported that intrastrand tetraplex formation takes place in a
nuclease hypersensitive element upstream of the human c-myc proto-oncogene.
Despite the highly repetitive guanine-rich sequence of the hypersensitive
element, fluorescence resonance energy transfer measurements indicate that
only one well defined tetraplex structure forms therein. The proposed struc
ture, which is specifically stabilized by potassium ions in vitro, has a co
re of three stacked guanine tetrads that is capped by two intrastrand A-T b
ase pairs.