title: Guanine-vacancy-bearing G-quadruplexes responsive to guanine derivatives.
abstract: G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and nanodevices. G-quadruplexes are normally composed of four Gn (n ≥ 3) tracts assembled into a core of multiple stacked G-quartet layers. By dimethyl sulfate footprinting, circular dichroism spectroscopy, thermal melting, and photo-cross-linking, here we describe a unique type of intramolecular G-quadruplex that forms with one G2 and three G3 tracts and bears a guanine vacancy (G-vacancy) in one of the G-quartet layers. The G-vacancy can be filled up by a guanine base from GTP or GMP to complete an intact G-quartet by Hoogsteen hydrogen bonding, resulting in significant G-quadruplex stabilization that can effectively alter DNA replication in vitro at physiological concentration of GTP and Mg(2+). A bioinformatic survey shows motifs of such G-quadruplexes are evolutionally selected in genes with unique distribution pattern in both eukaryotic and prokaryotic organisms, implying such G-vacancy-bearing G-quadruplexes are present and play a role in gene regulation. Because guanine derivatives are natural metabolites in cells, the formation of such G-quadruplexes and guanine fill-in (G-fill-in) may grant an environment-responsive regulation in cellular processes. Our findings thus not only expand the sequence definition of G-quadruplex formation, but more importantly, reveal a structural and functional property not seen in the standard canonical G-quadruplexes.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
authors.forename: Xin-min
authors.initials: XM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China; zhengkewei@ioz.ac.cn z.tan@ioz.ac.cn.
authors.forename: Ke-wei
authors.initials: KW
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
authors.forename: Jia-yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
authors.forename: Hong-he
authors.initials: HH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
authors.forename: Yi-de
authors.initials: YD
authors.lastname: He
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: Bi-feng
authors.initials: BF
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China;
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China; zhengkewei@ioz.ac.cn z.tan@ioz.ac.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D004261:DNA Replication; D054856:G-Quadruplexes; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D006147:Guanine; D004247:DNA
keywords: G-quadruplex; G-vacancy; guanine-responsive; nucleic acids