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J Am Chem Soc. 2019 May 15;141(19):7758-7764. doi: 10.1021/jacs.8b13855. Epub 2019 Apr 26.

Topologically Constrained Formation of Stable Z-DNA from Normal Sequence under Physiological Conditions.

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College of Food Science and Engineering , Ocean University of China , No. 5 Yushan Road , Qingdao , People's Republic of China.
Laboratory for Marine Drugs and Bioproducts , Qingdao National Laboratory for Marine Science and Technology , No. 1 Wenhai Road , Qingdao , People's Republic of China.


Z-DNA, a left-handed duplex, has been shown to form in vivo and regulate expression of the corresponding gene. However, its biological roles have not been satisfactorily understood, mainly because Z-DNA is easily converted to the thermodynamically favorable B-DNA. Here we present a new idea to form stable Z-DNA under normal physiological conditions and achieve detailed analysis on its fundamental features. Simply by mixing two complementary minicircles of single-stranded DNA with no chemical modification, the hybridization spontaneously induces topological constraint which twines one-half of the double-stranded DNA into stable Z-DNA. The formation of Z-conformation with high stability has been proved by using circular dichroism spectroscopy, Z-DNA-specific antibody binding assay, nuclease digestion, etc. Even at a concentration of MgCl2 as low as 0.5 mM, Z-DNA was successfully obtained, avoiding the use of high salt conditions, limited sequences, ancillary additives, or chemical modifications, criteria which have hampered Z-DNA research. The resultant Z-DNA has the potential to be used as a canonical standard sample in Z-DNA research. By using this approach, further developments of Z-DNA science and its applications become highly promising.


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