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

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 ¹H-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.

Keywords:

• hTERT
• intron 6
• NMR
• quadruplex

Acknowledgments

This work is supported by Italian M.U.R.S.T. and Regione Campania (L.41, L.5).