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Tuesday, March 4, 2008

Mechanism: B to Z DNA Transition

DNA can change its shape to achieve its purposes in life. Z DNA was thought to be an inherently unstable. It was the first non-B form of DNA to be discovered. It contains an alternating sequence of purine and pyrimidine.The orientation of its H-bonded base pairs are turned upside down. Unlike A or B DNA, Z DNA is a left handed helix composed of base pairs in which each of the purines has undergone a rotation from the anti- to syn- conformation.The sequence of DNA strands that form duplexes adopting the Z conformation must alternate purines with pyrimidines (i.e. GCGCGC), and the solvent conditions must usually include high ionic strength or high concentrations of organic solvent. Although the low-energy forms of right-handed duplexes of B-DNA and A-RNA are structurally very different, they adopt similar left-handed Z-conformations (Nakamura et. al,1995).

The discovery of Za protein that specifically binds to Z DNA implicated that this form as a biologically functional DNA component. Today, Za is used to locate B-Z junction. The B-Z junction is the connection between the two forms of DNA.B-Z junction have this orientation major groove of B-DNA joins to the minor groove of Z-DNA whereas the minor groove of B-DNA joins with the major groove of Z-DNA.

Ha et al(2005) group suggested based on the experiments the most acceptable model of B to Z DNA transition that Z DNA formation might start with the breakage a single bp(2 N bases) in the B form then it will swing round at 180 and re-pair Z DNA conformation then the process would continue from the initiation point either unidirectionally or bidirectionally until the entire track is transformed it to Z-DNA helix.The breakage of single bp otherwise known as base extrusion is a well known scheme used by enzymes that edit or repair DNA.Base extrusion can be triggered when the DNA is exposed to extreme conditions like high temperature and also by mutation. The chance of A-T and G-C to be extruded is assumed to be equal. The base pairs with respective B to Z helices retain their standard A-T and G-C base pairing and stacking. Due to the discovery of B-Z junction it is reasonable to believe that Z DNA is stable and energetically feasible and due to the advancement of Molecular Genetics and Biophysics additional roles of Z-DNA is expected to emerge.

References

Ha,et.al(2005).Nature

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