title: Structure of human telomeric DNA in crowded solution.
abstract: G-quadruplex structures formed by DNA at the human telomeres are attractive anticancer targets. Human telomeric sequences can adopt a diverse range of intramolecular G-quadruplex conformations: a parallel-stranded conformation was observed in the crystalline state, while at least four other forms were seen in K(+) solution, raising the question of which conformation is favored in crowded cellular environment. Here, we report the first NMR structure of a human telomeric G-quadruplex in crowded solution. We show that four different G-quadruplex conformations are converted to a propeller-type parallel-stranded G-quadruplex in K(+)-containing crowded solution due to water depletion. This study also reveals the formation of a new higher-order G-quadruplex structure under molecular crowding conditions. Our molecular dynamics simulations of solvent distribution provide insights at molecular level on the formation of parallel-stranded G-quadruplex in environment depleted of water. These results regarding human telomeric DNA can be extended to oncogenic promoters and other genomic G-rich sequences.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Brahim
authors.initials: B
authors.lastname: Heddi
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011188:Potassium; D012996:Solutions; D016615:Telomere / Q000235:genetics*
chemical_list: D012996:Solutions; D004247:DNA; D011188:Potassium