Left-handed Z-DNA has a Sister? The Homoduplex d(A-G)n
The conformational polymorphism of DNA primarily reflects the sequence and the influence of environmental conditions. Homopurine sequences are highly polymorphic; alpha-helical, hairpin, duplexes, triplexes, and tetraplex structures have been described in the extensive literature on the subject. The composition and concentrations of the supporting electrolyte, especially multivalent cations, and pH are important factors. Such simple sequences are not simply laboratory curiosities. Alternating d(A-G) is highly abundant in higher vertebrates (primate and rodents) and is thought to intervene in recombination, gene expresion and the stabilization of genomic structure.
We have demonstrated previously  that the prevalent form of poly d(A-G) at neutral pH and in the presence of Mg cations is a parallel-stranded double helix based on AA and GG base pairs. However, the structural features of the proposed duplex have remained obscure, perhaps due in part to the polymorphism that has prevented elucidation by high resolution NMR or crystallographic analysis. Force field calculations [2,3] with sugar residues in anti suggest that both left- and right-handed conformations are possible. Interestingly the left-handed model appears to be the more stable structure.
Recently, we developed a method based on fluorescence resonance energy tranfer to determine the helical handedness, rise and twist of different DNA conformations . The technique requires the design of a set of molecules consisting of two fused helical segments, one of which is in a known reference helical form. The duplexes are covalently labeled at one end with a donor and at the other with an acceptor. By systematically shifting the position of the junction while maintaining constant the total length in base pairs, the variation in the efficiency of energy transfer can be shown to depend primarily and sensitively on the differences in helical twist and rise of the two constituent segments. Using a reference molecule which could adopt either a B- or Z- conformation the helical parameters of a ps-AT DNA was estimated. In the present work, we investigated the helical handedness (helical parameters) of the ps-(A-G)n motif using the FRET technique.
In the event that the left-handed form of d(A-G)n is confirmed, it would imply that a DNA duplex second only to B-DNA in stability under physiological salt conditions is non-canonical in all 3 fundamental features of secondary structure: strand orientation, base pairing, and helical sense. Z-DNA, move over.
1. K. Rippe, V. Fritsch, E. Westhof, and T.M. Jovin. Alternating d(G-A) sequences form a
parallel-stranded DNA homoduplex EMBO J. 11, 3777 (1992).
*Present address: Dept. of Organic Chemistry, Univ. of Buenos Aires;
T. M. Jovin, E. A. Jares-Erijman*, V. V. Kuryavyi**, and R. Klement
Department of Molecular Biology
Max Planck Institute for Biophysical Chemistry