Z-DNA - AbsoluteAstronomy.com

Z-DNA is one of the many possible double helical structures of DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. 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-

A-DNA

A-DNA is one of the many possible double helical structures of DNA. A-DNA is thought to be one of three biologically active double helical structures along with B- and Z-DNA. It is a right-handed double helix fairly similar to the more common and well-known B-DNA form, but with a shorter more...

and B-DNA.

History

Z-DNA was the first single-crystal X-ray structure of a DNA fragment (a self-complementary DNA hexamer d(CG)₃). It was resolved as a left-handed double helix with two anti-parallel chains that were held together by Watson-Crick base pairs (see: x-ray crystallography

X-ray crystallography

X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

). It was solved by Andrew Wang, Alexander Rich

Alexander Rich

Alexander Rich, MD is a biologist and biophysicist. He is the William Thompson Sedgwick Professor of Biophysics at MIT and Harvard Medical School. Dr. Rich earned both an A.B. and an M.D. from Harvard University. He was a post-doc of Linus Pauling along with James Watson...

, and co-workers in 1979 at MIT

Massachusetts Institute of Technology

The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...

. The crystallisation of a B- to Z-DNA junction in 2005 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

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

.

In 2007, the RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

version of Z-DNA, Z-RNA, was described as a transformed version of an A-RNA double helix into a left-handed helix.
The transition from A-RNA to Z-RNA, however, was already described in 1984.

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

Purine

A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

-pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

sequence (especially poly(dGC)₂), negative DNA supercoil

DNA supercoil

DNA supercoiling refers to the over- or under-winding of a DNA strand, and is an expression of the strain on the polymer. Supercoiling is important in a number of biological processes, such as compacting DNA. Additionally, certain enzymes such as topoisomerases are able to change DNA topology to...

ing or high salt and some cations (all at physiological temperature, 37°C, and pH 7.3-7.4). Z-DNA can form a junction with B-DNA (called a "B-to-Z junction box") in a structure which involves the extrusion of a base pair. The Z-DNA conformation has been difficult to study because it does not exist as a stable feature of the double helix. Instead, it is a transient structure that is occasionally induced by biological activity and then quickly disappears.

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).

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. 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

Chromosome 22 (human)

Chromosome 22 is one of the 23 pairs of chromosomes in human cells. Humans normally have two copies of Chromosome 22 in each cell. Chromosome 22 is the second smallest human chromosome, spanning about 49 million DNA base pairs and representing between 1.5 and 2 % of the total DNA in cells.In 1999,...

with a selected set of known gene transcription sites

Transcription (genetics)

Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

suggests there is a correlation.

Z-DNA formed after transcription initiation. The first domain to bind Z-DNA with high affinity was discovered in ADAR1 using an approach developed by Alan Herbert
. Crystallographic and NMR studies confirmed the biochemical findings that this domain bound Z-DNA in a non-sequence-specific manner . Related domains were identified in a number of other proteins through sequence homology
. The identification of the Z-alpha domain provided a tool for other crystallographic stuides that lead to the characterization of Z-RNA and the B-Z junction. Biological studies suggested that the Z-DNA binding domain of ADAR1 may loalize this enzyme that modifies the sequence of the newly formed RNA to sites of active transcription.

In 2003, Biophysicist Alexander Rich of the Massachusetts Institute of Technology noticed that a poxvirus virulence factor, called E3L that has a Z-alpha related domain, mimicked a mammalian protein that binds Z-DNA. In 2005, Rich and his colleagues pinned down what E3L does for the poxvirus. When expressed in human cells, E3L increases by five- to 10-fold the production of several genes that block a cell’s ability to self-destruct in response to infection.

Rich speculates that the Z-DNA is necessary for transcription and that E3L stabilizes the Z-DNA, thus prolonging expression of the anti-apoptotic genes. He suggests that a small molecule that interferes with the E3L binding to Z-DNA could thwart the activation of these genes and help protect people from pox infections.

Comparison Geometries of Some DNA Forms

Geometry attribute	A-form	B-form	Z-form
Helix sense	right-handed	right-handed	left-handed
Repeating unit	1 bp	1 bp	2 bp
Rotation/bp	32.7°	35.9°	60°/2
bp/turn	11	10.5	12
Inclination of bp to axis	+19°	−1.2°	−9°
Rise/bp along axis	2.3 Å (0.23 nm)	3.32 Å (0.332 nm)	3.8 Å (0.38 nm)
Pitch/turn of helix	28.2 Å (2.82 nm)	33.2 Å (3.32 nm)	45.6 Å (4.56 nm)
Mean propeller twist	+18°	+16°	0°
Glycosyl angle	anti	anti	C: anti, G: syn
Sugar pucker	C3'-Y	C2'-M	C: C2'-C, G: C3'-A
Diameter	23 Å (2.3 nm)	20 Å (2.0 nm)	18 Å (1.8 nm)
Sources:

External links

ZHunt Online Server