Structural insight into the hTERT intron 6 sequence d(GGGGTGAAAGGGG) from 1H-NMR study.
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.
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Napoli, Italy.
Ada
A
Virno
Luciano
L
Mayol
Andres
A
Ramos
Franca
F
Fraternali
Bruno
B
Pagano
Antonio
A
Randazzo
D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D007438:Introns; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D004247:DNA; D019098:Telomerase