title: Human telomeric DNA sequence-specific cleaving by G-quadruplex formation.
abstract: 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.
authors.affiliation: 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
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuta
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tuomas
authors.initials: T
authors.lastname: Lönnberg
authors.forename: Makoto
authors.initials: M
authors.lastname: Komiyama
mesh_terms: 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
chemical_list: D015342:DNA Probes; D005029:Ethylenediamines; D063065:Organophosphonates; C418473:ethylenediaminetetrakis(methylphosphonic) acid; D002563:Cerium; D004247:DNA