Section 23.3.3.7. `Watson–Crick' Z-DNA

Ansevin & Wang (1990) have proposed an alternative left-handed double helix, with many of the properties of Z-DNA, but possessing the same backbone chain orientations as A- and B-DNA. With such a helix, a B-to-Z conversion would require only a twisting of the duplex about its axis – no separation of bases or unpairing, and no pulling apart of the stack. Ansevin & Wang did not challenge the X-ray crystal structure analyses of short Z-DNA oligomers. Instead, they suggested that Z-DNA was globally the most stable form, adopted in short oligomers where chain unravelling and rearrangement is easy, but that their `Watson–Crick' Z-DNA or Z(WC)-DNA was the structure that was actually produced by in vitro or in vivo manipulations of long DNA duplexes. They noted that most solution measurements focus on only two characteristics of the DNA: left-handedness and a dinucleotide repeat, both shared by Z-DNA and Z(WC)-DNA.

The Z(WC) helix is shown in Fig. 23.3.3.7, and a different stereo view appears as Fig. 7 of Dickerson (1992). Like Z-DNA, it is left-handed, with a deep minor groove and shallow major groove. Cytosines with anti glycosyl bonds and guanines with syn bonds alternate along each backbone strand. However, sugar puckering is reversed: cytosines are C3′-endo, while guanines are C2′-endo. In Z-DNA, the backbone chain runs parallel to the helix axis past G, and at right angles to the axis past C. In Z(WC)-DNA, this is reversed: parallel to the helix past C, and at right angles past G. Because of efficient stacking of base pairs, the logical two-base-pair structural unit in Z-DNA is ^5′C–G^3′; in Z(WC)-DNA it is ^5′G–C^3′. One such unit is clearly visible in the centre of Fig. 23.3.3.7. This behaviour is reflected in local twist angles: The Ansevin–Wang helix has been sedulously ignored since its publication in 1990, especially by crystallographers. The Science Citation Index lists an average of one citation of their paper per year since publication, most commonly by spectroscopists. Ho & Mooers (1996) are almost alone among crystallographers in coupling the B-to-Z interconversion dilemma to the possible existence of a different kind of left-handed structure in long polynucleotides. Of course the Z(WC)-DNA structure, as presented here, is only a model; it could be far from the true structure in many respects. But its interest lies in the fact that a left-handed alternating helix with `standard' backbone dirctions can be built with reasonable bond geometries and with properties that fit the various physical measurements as well as Z-DNA. It calls into question not the correctness of the Z-DNA structure obtained from short oligomers with free helix ends, but the relevance of that structure to the production of left-handed regions in longer duplexes with constrained ends.

Figure 23.3.3.7| top | pdf | Z(WC)-DNA, or `Watson–Crick Z-DNA', a proposed left-handed, zigzag, alternating purine/pyrimidine helix with many of the properties of Z-DNA, but with the backbone chain sense found in A- and B-DNA (Ansevin & Wang, 1990). Coordinates courtesy of Allen T. Ansevin.