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The catalytic subunit of human telomerase, hTERT, actively elongates the 3' end of the telomere in most cancer cells. The hTERT promoter, which contains many guanine-rich stretches on the same DNA strand, exhibits an exceptional potential for G-quadruplex formation. Here we show that one particular G-rich sequence in this region coexists in two G-quadruplex conformations in potassium solution: a (3 + 1) and a parallel-stranded G-quadruplexes. We present the NMR solution structures of both conformations, each comprising several robust structural elements, among which include the (3 + 1) and all-parallel G-tetrad cores, single-residue double-chain-reversal loops, and a capping A.T base pair. A combination of NMR and CD techniques, complemented with sequence modifications and variations of experimental condition, allowed us to better understand the coexistence of the two G-quadruplex conformations in equilibrium and how different structural elements conspire to favor a particular form.
Lim et al. (Thu,) studied this question.