Alternative DNA Structures
Gene expression and transcription can be influenced by changes of DNA topology. However, this type of control of gene expression is relatively universal and non specific.Thus, it is more suitable for permanent suppression of transcription, e.g., in genes that are expressed only in certain tissues or are active only during the embroyonic period and later become permanently inactive.
A. Three forms of DNA
The DNA double helix does not occur as a single structure, but rather represents a structural family of different types. The original classic form, determined by Watson and Crick in 1953, is B-DNA. The essential structural characteristic of B-DNA is the formation of two grooves, one large (major groove) and one small (minor groove). There are at least two further, alternative forms of the DNA double helix, Z-DNA and the rare form A-DNA. While B-DNA forms a right-handed helix, Z-DNA shows a left-handed conformation. This leads to a greater distance (0.77nm) between the base pairs than in B-DNA and a zig zag form(thus the designation Z-DNA). A-DNA is rare. It exists only in the dehydrated state and differs from the B form by a 20-degree rotation of the perpendicular axis of the helix. A-DNA has a deep major groove and a flat minor groove (Figures from Watson et al, 1987).
B. Major and minor grooves in B-DNA
The base pairing in DNA (adenine–thymine and guanine–cytosine) leads to the formation of a large and a small groove because the glycosidic bonds to deoxyribose (dRib) are not diametrically opposed. In B-DNA, the purine and pyrimidine rings lie 0.34 nm apart. DNA has ten base pairs per turn of the double helix. The distance from one complete turn to the next is 3.4 nm. In this way, localized curves arise in the double helix. The result is a somewhat larger and a somewhat smaller groove. <fn>Stryer, L.: Biochemistry, 4 th ed. W.H. Freeman & Co., New York, 1995.</fn>
C. Transition from B-DNA to Z-DNA
B-DNA is a perfect regular double helix except that the base pairs opposite each other do not lie exactly at the same level. They are twisted in a propeller-like manner. In this way, DNA can easily be bent without causing essential changes in the local structures. In Z-DNA the sugar–phosphate skeleton has a zigzag pattern; the single Z-DNA groove has a greater density of negatively charged molecules. Z-DNA may occur in limited segments in vivo. A segment of B-DNA consisting of GC pairs can be converted into Z-DNA when the bases are rotated 180 degrees. Normally, Z-DNA is thermodynamically relatively unstable. However, transition to Z-DNA is facilitated when cytosine is methylated in position 5 (C5). The modification of DNA by methylation of cytosine is frequent in certain regions of DNA of eukaryotes.Therearespecificproteinsthatbind to Z-DNA, but their significance for the regulation of transcription is not clear. <fn>Watson, J.D. et al.: Molecular Biology of the Gene. 3rd ed. Benjamin/Cummings Publishing Co., Menlo Park, California, 1987.</fn>