title: Formation of (3+1) G-quadruplexes with a long loop by human telomeric DNA spanning five or more repeats.
abstract: Structural studies of human telomeric repeats represent an active field of research with potential applications toward the development of specific telomeric quadruplex-targeting drugs for anticancer treatment. To date, high-definition structures were limited to DNA sequences containing up to four GGGTTA repeats. Here we investigate the formation of G-quadruplexes in sequences spanning five to seven human telomeric repeats using NMR, UV, and CD spectroscopy. A (3+1) G-quadruplex with a long propeller loop was isolated from a five-repeat sequence utilizing a guanine-to-inosine substitution. A simple approach of selective site-specific labeling of guanine residues was devised to rigorously determine the folding topology of the oligonucleotide. The same scaffold could be extrapolated to six- and seven-repeat sequences. Our results suggest that long human telomeric sequences consisting of five or more GGGTTA repeats could adopt (3+1) G-quadruplex structures harboring one or more repeat(s) within a single loop. We report on the formation of a Watson-Crick duplex within the long propeller loop upon addition of the complementary strand, demonstrating that the long loop could serve as a new recognition motif.
authors.affiliation: School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
authors.forename: Doris Jia En
authors.initials: DJ
authors.lastname: Yue
authors.forename: Kah Wai
authors.initials: KW
authors.lastname: Lim
authors.forename: Anh Tuân
authors.initials: AT
authors.lastname: Phan
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000737:chemistry*
chemical_list: D004247:DNA