title: Dissecting the strand folding orientation and formation of G-quadruplexes in single- and double-stranded nucleic acids by ligand-induced photocleavage footprinting.
abstract: The widespread of G-quadruplex-forming sequences in genomic DNA and their role in regulating gene expression has made G-quadruplex structures attractive therapeutic targets against a variety of diseases, such as cancer. Information on the structure of G-quadruplexes is crucial for understanding their physiological roles and designing effective drugs against them. Resolving the structures of G-quadruplexes, however, remains a challenge especially for those in double-stranded DNA. In this work, we developed a photocleavage footprinting technique to determine the folding orientation of each individual G-tract in intramolecular G-quadruplex formed in both single- and double-stranded nucleic acids. Based on the differential photocleavage induced by a ligand tetrakis(2-trimethylaminoethylethanol) phthalocyaninato zinc tetraiodine (Zn-TTAPc) to the guanines between the two terminal G-quartets in a G-quadruplex, this method identifies the guanines hosted in each terminal G-quartets to reveal G-tract orientation. The method is extremely intuitive, straightforward, and requires little expertise. Besides, it also detects G-quadruplex formation in long single- and double-stranded nucleic acids.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
authors.forename: Ke-wei
authors.initials: KW
authors.lastname: Zheng
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Li-xia
authors.initials: LX
authors.lastname: Zhang
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Hao
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
mesh_terms: D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles; D008024:Ligands; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D055668:Photochemical Processes / Q000187:drug effects*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D016615:Telomere / Q000235:genetics; D017967:Zinc Compounds
chemical_list: D004277:DNA, Single-Stranded; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D009942:Organometallic Compounds; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D019009:Proto-Oncogene Proteins c-kit