Coexistence of two distinct G-quadruplex conformations in the hTERT promoter

J Am Chem Soc. 2010 Sep 8;132(35):12331-42. doi: 10.1021/ja101252n.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • G-Quadruplexes*
  • GC Rich Sequence
  • Humans
  • Magnetic Resonance Spectroscopy
  • Nucleic Acid Conformation
  • Promoter Regions, Genetic*
  • Telomerase / chemistry*
  • Telomerase / metabolism
  • Telomere / chemistry


  • TERT protein, human
  • Telomerase