SELF-ASSOCIATION OF A DNA LOOP CREATES A QUADRUPLEX - CRYSTAL-STRUCTURE OF D(GCATGCT) AT 1.8-ANGSTROM RESOLUTION

The flexibility of DNA enables it to adopt three interconvertible type s of duplex termed the A-, B and Z-forms. It can also produce hairpin loops, tripler structures and guanine-rich quadruplex structures. Conf ormational flexibility assists in the tight packaging of DNA, for exam ple in chromosomes. This is important given the large quantity of gene tic information that must be packaged efficiently. Moreover, the abili ty of DNA to specifically self-associate or interact with complementar y sequences is fundamental to many biological processes. Structural st udies provide information about DNA conformation and DNA-DNA interacti ons and suggest features that might be relevant to how the molecule pe rforms its biological role. Results: We have characterized the structu re of a synthetic heptanucleotide that folds into a novel loop structu re. The loop is stabilized by association with a cation, by intra-stra nd hydrogen bonds between guanine and cytosine that are distinct from the normal Watson-Crick hydrogen bonds, and by van der Waals interacti ons. Two loops associate through the formation of four G . C pairs tha t exhibit pronounced base-stacking interactions. The formation of a sy mmetric A . A base pair further stabilizes loop dimerization. Stacking of the A . A pair on a symmetry-related A . A pairing assists the for mation of a four-stranded assembly. A T . T pairing is also observed b etween symmetry-related loops.Conclusions: This analysis provides a ra re example of an experimentally determined non-duplex DNA structure. I t provides conformational detail relevant to the tight packaging or fo lding of a DNA strand and illustrates how a cation might modulate phos phate-phosphate repulsion in a tightly packed structure. The observati on of base quartets involving G C base pairs suggests a further struct ure to be considered in DNA-DNA interactions. The structure also provi des detailed geometries for A . A and T . T base pairs.