Four-Stranded DNA Structures Can Be Stabilized by Two Different Types of Minor Groove G:C:G:C Tetrads

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• 作者：Nú ; ria Escaja ; Irene Gó ; mez-Pinto ; Enrique Pedroso ; Carlos Gonz&aacute ; lez
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：February 21, 2007
• 年：2007
• 卷：129
• 期：7
• 页码：2004 - 2014
• 全文大小：612K
• 年卷期：v.129,no.7(February 21, 2007)
• ISSN：1520-5126

文摘

Four-stranded nucleic acid structures are central to many processes in biology and insupramolecular chemistry. It has been shown recently that four-stranded DNA structures are not only limitedto the classical guanine quadruplex but also can be formed by tetrads resulting from the association ofWatson-Crick base pairs. Such an association may occur through the minor or the major groove side ofthe base pairs. Structures stabilized by minor groove tetrads present distinctive features, clearly differentfrom the canonical guanine quadruplex, making these quadruplexes a unique structural motif. Within ourefforts to study the sequence requirements for the formation of this unusual DNA motif, we have determinedthe solution structure of the cyclic oligonucleotide d<pCCGTCCGT&gt; by two-dimensional NMR spectroscopyand restrained molecular dynamics. This molecule self-associates, forming a symmetric dimer stabilizedby two G:C:G:C tetrads with intermolecular G-C base pairs. Interestingly, although the overall three-dimensional structure is similar to that found in other cyclic and linear oligonucleotides of related sequences,the tetrads that stabilize the structure of d<pCCGTCCGT&gt; are different to other minor groove G:C:G:Ctetrads found earlier. Whereas in previous cases the G-C base pairs aligned directly, in this new tetradthe relative position of the two base pairs is slipped along the axis defined by the base pairs. This is thefirst time that a quadruplex structure entirely stabilized by slipped minor groove G:C:G:C tetrads is observedin solution or in the solid state. However, an analogous arrangement of G-C base pairs occurs betweenthe terminal residues of contiguous duplexes in some DNA crystals. This structural polymorphism betweenminor groove GC tetrads may be important in stabilization of higher order DNA structures.