1.8.2 Z DNA

Unit 1 Structural variation in DNA reflects three things: the different possible conformations of the deoxyribose, rotation about the contiguous bonds that make up the phosphodeoxyribose backbone (Fig. 1.94 ), and free rotation about the C-1’–N-glycosyl bond (Fig.1.95). Because of steric constraints, purines in purine nucleotides are restricted to two stable conformations with respect to deoxyribose, called syn and anti (Fig. 1.5). Pyrimidines are generally restricted to the anti-conformation because of steric interference between the sugar and the carbonyl oxygen at C-2 of the pyrimidine In addition to the major B form, three additional DNA structures have been described. Two of these are compared to B DNA in Figure. In very low humidity, the crystallographic structure of B DNA changes to the A form; RNA-DNA and RNARNA helices exist in Figure 1.8.3 Watson-Crick model for the structure of DNA. The original this form in cells and in model proposed by Watson and Crick had 10 base pairs, or 34 Å (3.4 nm), vitro. per turn of the helix; subsequent measurements revealed 10.5 base pairs,

or 36 Å (3.6 nm), per turn. (a) Schematic representation, showing 1.8.2 Z DNA: dimensions of the helix. (b) Stick representation showing the backbone and

 Short DNA molecules stacking of the bases. (c) Space-filling model. composed of alternating purine-pyrimidine nucleotides (especially G s and Cs) adopt an alternative left-handed configuration instead of the normal right-handed helix. the bases seem to zigzag when viewed from the side.  Some evidence suggests that Figure 1.8.4 Structural variation in Z DNA may occur in cells, DNA. (a) The conformation of a although its function is nucleotide in unknown. DNA is affected by rotation about  Z-DNA is quite different from the right-handed forms. In fact, seven different bonds. Six of the bonds rotate freely. The limited rotation about bond 4 gives rise to Z-DNA is often compared ring pucker, in which one of the against B-DNA in order to atoms in the five-membered illustrate the major differences. furanose ring is out of the plane  The Z-DNA helix is left-handed described by the other four. This and has a structure that conformation is endo or exo, repeats every 2 base pairs. The major and minor grooves, depending on whether the atom is displaced to the same side of the plane as C-5 or to the opposite unlike A- and B-DNA, show side little difference in width.  Formation of this structure is generally unfavourable, although certain conditions can promote it; such as alternating purine-

Unit 1 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 Figure 1.8.5 Glycosidic Bond Configurations. For purine bases in involves the extrusion nucleotides, only two conformations with respect to the attached ribose  of a base pair. The Z-DNA units are sterically permitted, anti anti conformation or syn. Pyrimidines generally occur in the 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.

Biological significance

 It is 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  Toxic effect of ethidium bromide on trypanosomas is caused by shift of their kinetoplastid DNA to Z-form. The shift is caused by intercalation of EtBr and subsequent loosening of DNA structure that leads to unwinding of DNA, shift to Z-form and inhibition of DNA replication.  Z-DNA formed after transcription initiation  Z-DNA is necessary for transcription and prolonging expression of Figure 1.8.6 Comparison of A, B, and the anti-apoptotic genes. Z forms of DNA. For configuration values refer the table 1.8.1

Table 1.8.1 Difference between the A,B and Z forms of DNA

Geometry attribute A-form B-form

Helix sense

Repeating unit

Rotation/bp right-handed right-handed

1 bp

32.7 1 bp

35.9 Z-form

left-handed

2 bp

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'-endo C2'-endo C: C2'-endo, G: C3'-endo