Z-DNA

  Z-DNA is one of the many possible double helical structures of DNA. It is a left-handed double helical structure in which the double helix winds to the left in a zig-zag pattern (instead of to the right, like the more common B-DNA form). Z-DNA is thought to be one of three biologically active double helical structures along with A- and B-DNA.

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History

Z-DNA was the first crystal structure of a DNA molecule to be solved (see: x-ray crystallography). It was solved by Alexander Rich and co-workers in 1979 at MIT.^[1] The crystallisation of a B- to Z-DNA junction in 2005^[2] provided a better understanding of the potential role Z-DNA plays in cells. Whenever a segment of Z-DNA forms, there must be B-Z junctions at its two ends, interfacing it to the B-form of DNA found in the rest of the genome.

In 2007, the RNA version of Z-DNA was described as a transformed version of an A-RNA double helix into a left-handed helix.^[3]

Structure

  Z-DNA is quite different from the right-handed forms. In fact, Z-DNA is often compared against B-DNA in order to illustrate the major differences. The Z-DNA helix is left handed and has a structure that repeats every 2 base pairs. The major and minor grooves, unlike A- and B-DNA, show little difference in width. Formation of this structure is generally unfavourable, although certain conditions can promote it; such as alternating purine-pyrimidine sequence, DNA supercoiling or high salt and some cations. Z-DNA can form a junction with B-DNA in a structure which involves the extrusion of a base pair.

Predicting Z-DNA structure

It is possible to predict the likelihood of a DNA sequence forming a Z-DNA structure. An algorithm for predicting the propensity of DNA to flip from the B-form to the Z-form, ZHunt, was written by Dr. P. Shing Ho in 1984 (at MIT). This algorithm was later developed by Tracy Camp, P. Christoph Champ, Sandor Maurice, and Jeffrey M. Vargason for genome-wide mapping of Z-DNA (with P. Shing Ho as the principal investigator).^[4] Z-Hunt is available at Z-Hunt online.

Biological significance

While no definitive biological significance of Z-DNA has been found, it is commonly believed to provide torsional strain relief (supercoiling) while DNA transcription occurs.^[5][2] The potential to form a Z-DNA structure also correlates with regions of active transcription. A comparison of regions with a high sequence-dependent, predicted propensity to form Z-DNA in human chromosome 22 with a selected set of known gene transcription sites suggests there is a correlation.^[4]

Z-DNA formed after transcription initiation in some cases may be bound by RNA modifying enzymes which then alter the sequence of the newly-formed RNA [1].

Comparison Geometries of Some DNA Forms

References

1. ^ Wang AHJ, Quigley GJ, Kolpak FJ, Crawford JL, van Boom JH, Van der Marel G, Rich A (1979). "Molecular structure of a left-handed double helical DNA fragment at atomic resolution". Nature (London) 282: 680-686. PMID 514347
2. ^ ^{a b} Ha SC, Lowenhaupt K, Rich A, Kim YG, Kim KK (2005). "Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases". Nature 437: 1183-1186. PMID 16237447.
3. ^ Placido D, Brown BA 2nd, Lowenhaupt K, Rich A, Athanasiadis A (2007). "A left-handed RNA double helix bound by the Zalpha domain of the RNA-editing enzyme ADAR1". Structure 15 (4): 395-404. PMID 17437712.
4. ^ ^{a b} Champ PC, Maurice S, Vargason JM, Camp T, Ho PS (2004). "Distributions of Z-DNA and nuclear factor I in human chromosome 22: a model for coupled transcriptional regulation". Nucleic Acids Research 32 (22): 6501-6510. PMID 15598822.
5. ^ Rich A, Zhang S (2003). "Timeline: Z-DNA: the long road to biological function". Nature Rev Genet 4: 566–572.

Further reading

• Sinden RR (1994). DNA structure and function. Academic Press, 179-216. ISBN 0-12-645750-6
• Rich A, Zhang S (2003). Timeline: Z-DNA: the long road to biological function. Nat Rev Genet, 4:566–572.

See also

• Mechanical properties of DNA
• DNA
• A-DNA
• B-DNA