Z-DNA

Z-DNA
The Z-DNA structure.Proteopedia 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.

Contents

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). It was solved by Andrew Wang, 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, Z-RNA, was described as a transformed version of an A-RNA double helix into a left-handed helix.[3] The transition from A-RNA to Z-RNA, however, was already described in 1984.[4]

Structure

B-/Z-DNA junction bound to a Z-DNA binding domain. Note the two highlighted extruded bases. From PDB 2ACJ.

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 (especially poly(dGC)2), negative DNA supercoiling 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.[5] 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.[6]

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).[7] 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).[8]

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.[2][9] 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.[8]

Z-DNA formed after transcription initiation in some cases may be bound by RNA modifying enzymes, such as ADAR1[citation needed], which then alter the sequence of the newly formed RNA.[10]

In 2003, Biophysicist Alexander Rich of the Massachusetts Institute of Technology noticed that a poxvirus virulence factor, called E3L, mimicked a mammalian protein that binds Z-DNA.[11][12] 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

Side view of A-, B-, and Z-DNA.
The helix axis of A-, B-, and Z-DNA.
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°
Glycosyl angle anti anti C: anti,
G: syn
Sugar pucker C3'-endo C2'-endo C: C2'-endo,
G: C3'-endo
Diameter 23 Å (2.3 nm) 20 Å (2.0 nm) 18 Å (1.8 nm)
Sources:[13][14][15]

See also

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 (5740): 680–686. Bibcode 1979Natur.282..680W. doi:10.1038/282680a0. 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 (7062): 1183–1186. Bibcode 2005Natur.437.1183H. doi:10.1038/nature04088. 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. doi:10.1016/j.str.2007.03.001. PMC 2082211. PMID 17437712. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2082211. 
  4. ^ Hall K, Cruz P, Tinoco I Jr, Jovin TM, van de Sande JH (October 1984). "'Z-RNA'--a left-handed RNA double helix". Nature 311 (5986): 584–586. doi:10.1038/311584a0. PMID 6482970. 
  5. ^ de Rosa M, de Sanctis D, Rosario AL, Archer M, Rich A, Athanasiadis A, Carrondo MA (2010-05-18). "Crystal structure of a junction between two Z-DNA helices". Proc Natl Acad Sci USA 107 (20): 9088–9092. doi:10.1073/pnas.1003182107. PMC 2889044. PMID 20439751. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2889044. 
  6. ^ Zhang H, Yu H, Ren J, Qu X (2006). "Reversible B/Z-DNA transition under the low salt condition and non-B-form polydApolydT selectivity by a cubane-like europium-L-aspartic acid complex". Biophysical Journal 90 (9): 3203–3207. doi:10.1529/biophysj.105.078402. PMC 1432110. PMID 16473901. http://www.biophysj.org/cgi/content/full/90/9/3203. 
  7. ^ Ho PS, Ellison MJ, Quigley GJ, Rich A (1986). "A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences". EMBO Journal 5 (10): 2737–2744. PMC 1167176. PMID 3780676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1167176. 
  8. ^ 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 Res. 32 (22): 6501–6510. doi:10.1093/nar/gkh988. PMC 545456. PMID 15598822. http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=15598822. 
  9. ^ Rich A, Zhang S (2003). "Timeline: Z-DNA: the long road to biological function". Nature Review Genetics 4 (7): 566–572. doi:10.1038/nrg1115. PMID 12838348. 
  10. ^ Halber D (1999-09-11). "Scientists observe biological activities of 'left-handed' DNA". MIT News Office. http://web.mit.edu/newsoffice/1999/zdna-0911.html. Retrieved 2008-09-29. 
  11. ^ Kim YG, Muralinath M, Brandt T, Pearcy M, Hauns K, Lowenhaupt K, Jacobs BL, Rich A (2003). "A role for Z-DNA binding in vaccinia virus pathogenesis". Proc Natl Acad Sci USA 100 (12): 6974–6979. doi:10.1073/pnas.0431131100. PMC 165815. PMID 12777633. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=165815. 
  12. ^ Kim YG, Lowenhaupt K, Oh DB, Kim KK, Rich A (2004). "Evidence that vaccinia virulence factor E3L binds to Z-DNA in vivo: Implications for development of a therapy for poxvirus infection". Proc Natl Acad Sci USA 101 (6): 1514–1518. doi:10.1073/pnas.0308260100. PMC 341766. PMID 14757814. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=341766. 
  13. ^ Sinden, Richard R (1994-01-15). DNA structure and function (1st ed.). Academic Press. pp. 398. ISBN 0-12-645750-6. 
  14. ^ Rich A, Norheim A, Wang AHJ (1984). "The chemistry and biology of left-handed Z-DNA". Annual Review of Biochemistry 53 (1): 791–846. doi:10.1146/annurev.bi.53.070184.004043. PMID 6383204. 
  15. ^ Ho PS (1994-09-27). "The non-B-DNA structure of d(CA/TG)n does not differ from that of Z-DNA". Proc Natl Acad Sci USA 91 (20): 9549–9553. doi:10.1073/pnas.91.20.9549. PMC 44850. PMID 7937803. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=44850. 

External links


Wikimedia Foundation. 2010.

Игры ⚽ Нужно сделать НИР?

Look at other dictionaries:

  • DNA replication — DNA replication. The double helix is unwound and each strand acts as a template for the next strand. Bases are matched to synthesize the new partner strands. DNA replication is a biological process that occurs in all living organisms and copies… …   Wikipedia

  • DNA nanotechnology — seeks to make artificial, designed nanostructures out of nucleic acids, such as this DNA tetrahedron.[1] Each edge of the tetrahedron is a 20 base pair DNA double helix, and each vertex is a three arm junction. DNA n …   Wikipedia

  • DNA-encoded chemical library — DNA encoded chemical libraries (DEL) are a new technology for the synthesis and screening of collections of chemical compounds of unprecedented size and quality. DEL represents an advance in medicinal chemistry which bridges the fields of… …   Wikipedia

  • DNA nanoball sequencing — is a high throughput sequencing technology that is used to determine the entire genomic sequence of an organism. The method uses rolling circle replication to amplify small fragments of genomic DNA into DNA nanoballs. Fluorescent probes bind to… …   Wikipedia

  • DNA ligase — repairing chromosomal damage Identifiers EC number 6.5.1.1 …   Wikipedia

  • DNA computing — is a form of computing which uses DNA, biochemistry and molecular biology, instead of the traditional silicon based computer technologies. DNA computing, or, more generally, biomolecular computing, is a fast developing interdisciplinary area.… …   Wikipedia

  • DNA barcoding — is a taxonomic method that uses a short genetic marker in an organism s DNA to identify it as belonging to a particular species. It differs from molecular phylogeny in that the main goal is not to determine classification but to identify an… …   Wikipedia

  • DNA-Replikation — DNA Replikation. Die Doppelhelix wird durch die Helicase und die Topoisomerase geöffnet. Danach setzt die Primase einen Primer und die …   Deutsch Wikipedia

  • DNA condensation — refers to the process of compacting DNA molecules in vitro or in vivo.[1] Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems. Condensed DNA often has surprising properties,… …   Wikipedia

  • DNA mismatch repair — is a system for recognizing and repairing erroneous insertion, deletion and mis incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage.[1][2] Mismatch repair is strand… …   Wikipedia

  • DNA-Polymerase — Bänderdarstellung der DNA bindenden Domäne der humanen DNA Polymerase β …   Deutsch Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”