G-wires: The growth and characterization of a G4-DNA nanostructure

Abstract

<p>Guanine-rich sequences are vital components in the genomes of many organisms. For example, G-rich sequences are found in telomeres, fragile X locus, promoters, IgG switch regions, recombinational hot spots and the HIV RNA dimerization domain. The functions of these G-rich sequences rely in part on guanine self-recognition. G-rich sequences can adopt a quadruple helical conformation in the presence of specific monovalent and divalent metal cations which are also required for maintaining the quadruplex stability. The structural basis of the quadruplex is a cyclic Hoogsteen hydrogen bonded guanine tetrad known as the G-quartet. Sequences capable of forming G-quartets are classified as G-DNA. The family of G-DNA structures includes anti-parallel hairpin dimer conformations (G'2-DNA) and parallel tetramer conformations (G4-DNA). In this work we have employed the techniques of gel electrophoresis, UV spectroscopy and atomic force microscopy (AFM) to study a new G4-DNA nanostructure. The oligonucleotide d(GGGGTTGGGG) (Tet1.5) self-assembles into highly ordered filamentous polymers that we call G-wires. The self-assembly of Tet1.5 into G-wires is shown by gel electrophoresis to be highly ordered and dependent on specific metal cations. G-wires have characteristics that are unique to G-DNA. AFM analysis of G-wires complimented the electrophoretic studies and revealed the highly ordered structures to be filamentous polymers. G-wires exhibit resistance to distortion by the scanning probe that is related to their structural characteristics. This study indicates that G-wires could function as a scaffold enabling the controlled positioning of atoms and molecules in space, the primary goal of nanotechnology.</p>