Abstract

DNA sequences containing repetitive oligo-guanine sequences are observed in telomeric DNA and in recombination hotspots. In vitro, these sequences fold into at least two classes of unusual conformations involving the formation of guanine tetrads (G-quartets). Through the use of NMR, we have established that in solution in the presence of sodium ions, the oligodeoxynucleotide dTG 4T forms a parallel-stranded tatraplex, with hydrogen-bonded guanine tetrads. Here we present the detailed evidence for this configuration in 100 mM sodium ions at neutral pH. We show that the parallel-stranded tetraplex structure is stabilised relative to the single-strands when Na ions are replaced by K ions, without any evidence of significant change in those chemical shifts associated with the tetraplex form. We also present a model for the Na + solution structure of the tetraplex, by back-calculation from NOE volumes. We obtain excellent agreement with the data for structures with characteristics similar to B-DNA for the internal tetrads, G3 and G4. The outer tetrads, particularly the 5′-terminal G2, display some unstacking. We see no evidence for formation of thymine tetrads analogous to the uridine tetrads observed in RNA, but rather we find the terminal thymine conformations are not well determined by our data. We observe an uninterrupted cylindrical channel through the centre of the complex.

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