Human telomeric DNA sequence-specific cleaving by G-quadruplex formation.
Telomere is an emerging target for the treatment of human cancers. Here, we report a structure-based approach to sequence-specific cleaving of human telomeric DNA by G-quadruplex formation. Oligonucleotide with multiphosphonate [DNA-EDTP.Ce(IV)] at the 5' end binds to human telomere DNA by G-quadruplex formation and causes a sequence-specific strand break. These results provide the first proof of concept for targeting the human telomere DNA based on G-quadruplex formation, and this may serve as a starting point for the design of more efficient telomere sequence-specific cleaving reagents by G-quadruplex formation.
Xu
Yan
Y
Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan. xuyan@mkomi.rcast.u-tokyo.ac.jp
Suzuki
Yuta
Y
Lönnberg
Tuomas
T
Komiyama
Makoto
M
D002563:Cerium / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015342:DNA Probes / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D007700:Kinetics; D063065:Organophosphonates / Q000737:chemistry; D017422:Sequence Analysis, DNA / Q000379:methods; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D015342:DNA Probes; D005029:Ethylenediamines; D063065:Organophosphonates; C418473:ethylenediaminetetrakis(methylphosphonic) acid; D002563:Cerium; D004247:DNA