Z-DNA: the long road to biological function

  title={Z-DNA: the long road to biological function},
  author={Alexander Rich and Shuguang Zhang},
  journal={Nature Reviews Genetics},
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… 
The Structural and Functional Properties of Z-DNA
The most important result of this study is the demonstration of the presence of this form in eukaryotic DNA and its role in the regulation of gene transcription.
Topology in Biology: From DNA Mechanics to Enzymology
The focus of this contribution is on biological applications of topology to the study of DNA structure and to understanding protein–DNA interactions that involve alterations of DNA topology. We
Intrinsic Z-DNA is stabilized by the conformational selection mechanism of Z-DNA-binding proteins.
The results reveal that intrinsic Z-DNAs are dynamically formed and effectively stabilized by Z-DNA-binding proteins through efficient trapping of the Z conformation rather than being actively induced by them.
The Discovery of Z-DNA: the Work of Alexander Rich
The Effect of Anti-Z-DNA Antibodies on the B-DNA-Z DNA Equilibrium is studied to determine the carrier and removal status of these antibodies and their applications in medicine and materials science.
Z-DNA, an active element in the genome.
Accumulating experimental and clinical evidence support the idea that this non-B DNA conformation is involved in several important biological processes and may provide a target for the prevention and treatment of some human diseases.
DNA topology and transcription
Insight is provided into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and their possible involvement in gene transcription and emphasize recent studies that might inspire and impact future experiments on the involvement ofDNA topology in cellular functions.
DNA architecture: from G to Z.
Molecular biology: DNA twists and flips
The determination of the crystal structure of the junction between left-handed DNA and ‘normal’, right-handedDNA or B-DNA is determined, showing that the junction is very tight, and that a base pair is pushed out of the double helix, one base on each side of the Junction.
Incorporation of CC steps into Z-DNA: interplay between B-Z junction and Z-DNA helical formation.
A method for characterizing sequence-specific preferences for Z-DNA formation and B-Z junction localization within heterogeneous DNA duplexes is developed that is based on combining 2-aminopurine fluorescence measurements with a new quantitative application of circular dichroism spectroscopy for determining the fraction of B- versus Z- DNA.
Photochemical approach to probing different DNA structures.
The use of photochemical dehalogenation of 5-halouracil-containing DNA to probe the structure of DNA is discussed, suggesting that this photochemical approach could be applied as a probe of DNA conformations in living cells.


Z-DNA in transcriptionally active chromosomes.
The experiments indicate that Z-DNA forms are present in a specific set of sites on the native chromosomes of Drosophila hydei, and show that removal of chromosomal proteins by proteinase K has a strong influence on the level of anti-Z-DNA reactivity.
The in-vivo occurrence of Z DNA.
A model is proposed for a function for the B-Z transition in ensuring the correct pairing of homologous chromosomes during meiosis and evidence for the in-vivo occurrence of Z-DNA was not detected in plasmid DNA isolated from bacterial cells growing in the absence of protein synthesis inhibitors.
Identification of transcriptionally induced Z-DNA segments in the human c-myc gene.
Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes
This is the first identification of the Z-DNA conformation in material of biological origin and the staining is found in the interband regions and its intensity varies among different interbands in a reproducible manner.
Construction of a Z-DNA-specific restriction endonuclease.
Created Z alpha nuclease, a structure-specific restriction enzyme, may be a useful tool for further study of the biological role of Z-DNA, and cut has been mapped to the edge of the B-Z junction, suggesting that Z alphaNuclease binds within the Z- DNA insert, but cleaves in the nearby B-DNA.
‘Z-RNA’—a left-handed RNA double helix
Evidence is obtained by these different spectroscopic techniques that poly(G-C)·poly(C) undergoes a transition from the A-form to a left-handed Z-form in conditions of high ionic strength and at temperatures above 35°C, of relevance to the biological situations in which double-stranded RNA occurs.
Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA.
The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha, which is specific for left-handed Z- DNA, and the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.
Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA.
It is confirmed that dsRNA adenosine deaminase activity and Z-DNA binding are properties of the same molecule, which may indicate a distinctive mechanism of gene regulation that is, in part, dependent on DNA topology.
The level of Z-DNA in metabolically active, permeabilized mammalian cell nuclei is regulated by torsional strain
Permeabilized nuclei from mammalian cells encapsulated within agarose microbeads in an isotonic buffer were used to probe the extent of DNA negative supercoiling and the effects of altering torsional strain by binding radioactively labeled monoclonal antibodies to Z-DNA.
The sequence (dC-dA)n X (dG-dT)n forms left-handed Z-DNA in negatively supercoiled plasmids.
  • A. Nordheim, A. Rich
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1983
Z-DNA-specific antibodies have been used to demonstrate the formation of left-handed Z-DNA in sequences of (dC-dA)32 X (dG-dT)32 in negatively supercoiled plasmids. Z-DNA was found to form at