title: Structural characterization of quadruplex DNA with in-cell EPR approaches.
abstract: Guanosine-rich DNA sequences have the potential to adopt four-stranded conformations termed quadruplexes. The chromosomes of higher organisms are capped by so-called telomeres that are composed of repeats of the sequence TTAGGG. Up to 200 nucleotides of the G-rich strand form an overhang that is suspected to fold into intramolecular G-quadruplexes. Since induction of quadruplexes at the telomeres results in anti-proliferative effects, the intracellular structure of G-quadruplexes is of high interest as an anti-cancer drug target. Here we give a perspective on the elucidation of DNA sequence folds by electron paramagnetic resonance (EPR) distance measurements. The technique complements X-ray crystallography and NMR spectroscopy, as it can be applied in noncrystalline states, is not intrinsically limited by the size of the bio-macromolecular complex, and is able to analyze flexible structures or coexisting DNA conformation.
authors.affiliation: Department of Chemistry and Konstanz Research School of Chemical Biology, University of Konstanz, 78467 Konstanz, Germany.
authors.forename: Isabelle T
authors.initials: IT
authors.lastname: Holder
authors.forename: Malte
authors.initials: M
authors.lastname: Drescher
authors.forename: Jörg S
authors.initials: JS
authors.lastname: Hartig
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D013113:Spin Labels; D014982:Xenopus laevis
chemical_list: D013113:Spin Labels; D004247:DNA
keywords: EPR spectroscopy; Human telomeric quadruplex; Noncanonical nucleic acids; Site-directed spin-labeling