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Z-DNA: the long road to biological function


Biologists were puzzled by the discovery of left-handed Z-DNA because it seemed unnecessary. Z-DNA was stabilized by the negative supercoiling generated by transcription, which indicated a transient localized conformational change. Few laboratories worked on the biology of Z-DNA. However, the discovery that certain classes of proteins bound to Z-DNA with high affinity and great specificity indicated a biological role. The most recent data show that some of these proteins participate in the pathology of poxviruses.

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Figure 1: Discovery of Z-DNA.
Figure 2: Negative supercoiling stabilizes Z-DNA.
Figure 3: Transcription stabilizes Z-DNA.
Figure 4: The lethality of mice following intracerebral inoculation of 100 viral plaque-forming units of vaccinia virus constructs45.


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Correspondence to Shuguang Zhang.

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The editing enzyme double-stranded RNA adenosine deaminase, which converts adenine to inosine in pre-mRNA. This enzyme has an N-terminal domain that binds tightly to Z-DNA.


Nucleic-acid bases can rotate about the glycosyl bond. The Watson–Crick hydrogen-bonding atoms point away from the sugar in the anti-conformation (as in B-DNA), and have the opposite orientation in the syn-conformation. Purines can form the syn-conformation more easily than pyrimidines.


The random kinetic thermal motion of molecules.


X-rays are scattered by electrons and if a molecule has regular periodicities, they will be detected by the diffraction pattern. In this technique, DNA molecules are orientated so that their long axes are parallel. Although the diffraction pattern can provide some information about the molecule, the conclusions are often tentative because the number of reflections is relatively small.


This method measures the difference in absorption of right and left circularly polarized light as it passes through a solution containing molecules that absorb at that wavelength. The circular-dichroism spectrum is plotted as a function of wavelength.


A chromosome that has duplicated many times and has remained laterally associated so that it is visible, as seen in Drosophila salivary glands.


Measures the vibrations of molecules that are usually influenced by the conformation of a molecule. This can be obtained from crystalline materials as well as materials in solution.


In this technique, a molecule is crystallized to produce many repetitions that are organized in a regular three-dimensional array. This produces X-ray diffraction with a large number of reflections. Solution of the crystal structure can establish the conformation of the molecule because large amounts of redundant data are collected.

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Rich, A., Zhang, S. Z-DNA: the long road to biological function. Nat Rev Genet 4, 566–572 (2003).

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