The orientation of the ends of G-quadruplex structures investigated using end-extended oligonucleotides.
Human telomere DNA is of intense interest because of its role in the biology of both cancer and aging. The single-stranded telomere terminus can adopt the structure of a G-quadruplex, which is of particular important for anticancer drug discovery many researchers have reported various G-quadruplex structures in the human telomere. Although the human telomere consists of a number of tandem repeats, higher-order G-quadruplex structures are less discussed due to the complexity of the structures. Here we examined the orientation of the ends of the G-quadruplex structures with consideration given to higher-order structures. We prepared end-extended and (Br)G-substituted oligonucleotides. Native PAGE analysis, CD measurements and NMR spectroscopy showed that the ends of stable G-quadruplex structures point in opposite directions. Our results indicate that the human telomere DNA is likely to form rod-like higher-order structures. This may provide important information for understanding telomere structure and the development of telomere G-quadruplex-binding molecules as telomerase inhibitors.
Sannohe
Yuta
Y
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, Japan.
Sato
Kyosuke
K
Matsugami
Akimasa
A
Shinohara
Ken-ichi
K
Mashimo
Tomoko
T
Katahira
Masato
M
Sugiyama
Hiroshi
H
D001483:Base Sequence; D002942:Circular Dichroism; D004587:Electrophoresis, Agar Gel; D054856:G-Quadruplexes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry*
D009841:Oligonucleotides