We have discovered that single-stranded DNA containing short guanine-rich motifs will self-associate at physiological salt concentrations to make four-stranded structures in which the strands run in parallel fashion. We believe these complexes are held together by guanines bonded to each other by Hoogsteen pairing. Such guanine-rich sequences occur in immunoglobulin switch regions, in gene promoters, and in chromosomal telomeres. We speculate that this self-recognition of guanine-rich motifs of DNA serves to bring together, and to zipper up in register, the four homologous chromatids during meiosis.
A new class of catalytic activity for nucleic acids is reported. The aptamer-hemin complexes described are novel DNA enzymes and their study will help elucidate the structural and functional requirements of peroxidase enzymes in general and the ways that a nucleic acid 'apoenzyme' might work to enhance the intrinsic peroxidatic ability of hemin. These aptamer-hemin complexes could be regarded as prototypes for redox-catalyzing ribozymes in a primordial 'RNA world'.
Single-stranded complex guanine-rich DNA sequences from chromosomal telomeres and elsewhere can associate to form stable parallel four-stranded structures termed G4-DNA by a process that is anomalously dependent on the particular alkali metal cation that is present. The anomaly, which is not found in the formation of G4-DNA by oligonucleotides containing short, single runs of three or more guanines, is caused by potassium cations excessively stabilizing fold-back intermediate structures, or pathway by-products.
It has been proposed that guanine-rich DNA forms four-stranded structures in vivo called G-quadruplexes or G4 DNA. G4 DNA has been implicated in several biological processes, but tools to study G4 DNA structures in cells are limited. Here we report the development of novel murine monoclonal antibodies specific for different G4 DNA structures. We show that one of these antibodies designated 1H6 exhibits strong nuclear staining in most human and murine cells. Staining intensity increased on treatment of cells with agents that stabilize G4 DNA and, strikingly, cells deficient in FANCJ, a G4 DNA-specific helicase, showed stronger nuclear staining than controls. Our data strongly support the existence of G4 DNA structures in mammalian cells and indicate that the abundance of such structures is increased in the absence of FANCJ. We conclude that monoclonal antibody 1H6 is a valuable tool for further studies on the role of G4 DNA in cell and molecular biology.
A specific DNA oligonucleotide--hemin complex (PS2.M--hemin complex) that exhibits DNA-enhanced peroxidative activity was studied by EPR and UV--visible spectroscopy and by chemical probing analysis. EPR data obtained from low-temperature experiments on the PS2.M--hemin complex showed both a low-field g approximately 6 and a high-field g approximately 2 signal. These EPR signals are typical of high-spin ferric heme with axial symmetry as judged by the EPR spectrum of six-coordinate heme iron in acidic Fe(III)-myoglobin. This similarity is consistent with the presence of two axial ligands to the heme iron within the PS2.M--hemin complex, one of which is a water molecule. Optical analyses of the acid-base transition for the hemin complex yielded a pK(a) value for the water ligand of 8.70 +/- 0.03 (mean +/- SD). Low-temperature EPR analysis coupled with parallel spin-trapping investigations following the reaction of the PS2.M--hemin complex and hydrogen peroxide (H(2)O(2)) indicated the formation of a carbon-centered radical, most likely on the PS2.M oligonucleotide. Chemical probing analysis identified specific guanine bases within the PS2.M sequence that underwent oxidative damage upon reaction with H(2)O(2). These and other experimental findings support the hypothesis that the interaction of specific guanines of PS2.M with the bound hemin cofactor might contribute to the superior peroxidative activity of the PS2.M--hemin complex.
DNA has played an early and powerful role in the development of bottomup nanotechnologies, not least because of DNA's precise, predictable, and controllable properties of assembly on the nanometer scale. Watson−Crick complementarity has been used to build complex 2D and 3D architectures and design a number of nanometer-scale systems for molecular computing, transport, motors, and biosensing applications. Most of such devices are built with classical B-DNA helices and involve classical A-T/U and G-C base pairs. However, in addition to the above components underlying the iconic double helix, a number of alternative pairing schemes of nucleobases are known. This review focuses on two of these noncanonical classes of DNA helices: G-quadruplexes and the imotif. The unique properties of these two classes of DNA helix have been utilized toward some remarkable constructions and applications: G-wires; nanostructures such as DNA origami; reconfigurable structures and nanodevices; the formation and utilization of hemin-utilizing DNAzymes, capable of generating varied outputs from biosensing nanostructures; composite nanostructures made up of DNA as well as inorganic materials; and the construction of nanocarriers that show promise for the therapeutics of diseases.
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