Structural insight into the hTERT intron 6 sequence d(GGGGTGAAAGGGG) from 1H-NMR study

Nucleosides Nucleotides Nucleic Acids. 2007;26(8-9):1133-7. doi: 10.1080/15257770701521854.

Abstract

The interest in DNA quadruplex structures has been fueled by the recognition that telomeres, the 3' single stranded guanine-rich overhangs found at the termini of chromosomes, are likely to form G-tetrads type structures important in cell senescence and cancer. In addition to their presence in telomeres, where they may play a role in maintaining the stability and integrity of chromosomes, guanine-rich regions are found in other region of the genome, amongst these is intron 6 of hTERT a gene codifying for the enzyme telomerase. Interestingly, the formation of G-quadruplexes in this region is involved in the down-regulation of telomerase activity caused by an alteration of the hTERT splicing pattern. Therefore, we have analyzed several sequences of that intron by (1)H-NMR and CD spectroscopy, and we have found that the sequence d(GGGGTGAAAGGGG) is able to fold in a single well-defined antiparallel quadruplex structure consisting of four G-tetrads, possessing a twofold symmetry, and containing four Gs in a syn glycosidic conformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Circular Dichroism
  • DNA / chemistry*
  • DNA / genetics*
  • Humans
  • Introns*
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / genetics
  • Telomerase / genetics*

Substances

  • Oligodeoxyribonucleotides
  • DNA
  • Telomerase