title: Mutually Exclusive Formation of G-Quadruplex and i-Motif Is a General Phenomenon Governed by Steric Hindrance in Duplex DNA.
abstract: G-Quadruplex and i-motif are tetraplex structures that may form in opposite strands at the same location of a duplex DNA. Recent discoveries have indicated that the two tetraplex structures can have conflicting biological activities, which poses a challenge for cells to coordinate. Here, by performing innovative population analysis on mechanical unfolding profiles of tetraplex structures in double-stranded DNA, we found that formations of G-quadruplex and i-motif in the two complementary strands are mutually exclusive in a variety of DNA templates, which include human telomere and promoter fragments of hINS and hTERT genes. To explain this behavior, we placed G-quadruplex- and i-motif-hosting sequences in an offset fashion in the two complementary telomeric DNA strands. We found simultaneous formation of the G-quadruplex and i-motif in opposite strands, suggesting that mutual exclusivity between the two tetraplexes is controlled by steric hindrance. This conclusion was corroborated in the BCL-2 promoter sequence, in which simultaneous formation of two tetraplexes was observed due to possible offset arrangements between G-quadruplex and i-motif in opposite strands. The mutual exclusivity revealed here sets a molecular basis for cells to efficiently coordinate opposite biological activities of G-quadruplex and i-motif at the same dsDNA location.
authors.affiliation: Department of Chemistry and Biochemistry and School of Biomedical Sciences, Kent State University , Kent, Ohio 44242, United States.
authors.forename: Yunxi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University , Tianjin 300071, China.
authors.forename: Deming
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Chemistry and Biochemistry and School of Biomedical Sciences, Kent State University , Kent, Ohio 44242, United States.
authors.forename: Chiran
authors.initials: C
authors.lastname: Ghimire
authors.affiliation: Department of Chemistry and Biochemistry and School of Biomedical Sciences, Kent State University , Kent, Ohio 44242, United States.|MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-Sen University , Guangzhou 510275, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Chemistry and Biochemistry and School of Biomedical Sciences, Kent State University , Kent, Ohio 44242, United States.
authors.forename: Hanbin
authors.initials: H
authors.lastname: Mao
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D054856:G-Quadruplexes; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013237:Stereoisomerism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA