Human RNA editing enzyme, ADAR1, has two Z-DNA binding domains, Zα and Zβ, and preferentially binds Z-DNA rather than B-DNA. The crystal structural study revealed that one Zα protein binds to one strand of 6-bp CG-repeat DNA duplex and a second Zα binds to the opposite strand with 2-fold symmetry with respect to helical axis. Z-DNA is able to be produced in a long genomic DNA through formation of two B-Z junctions. We have performed NMR experiments on various Z-DNA complexed with Zα domain of human ADAR1. Our NMR study suggested the active B-Z transition mechanism in which the Zα first binds to B-DNA and then converts it to Z-DNA, a conformation that is then stabilized by the additional binding of a second Zα. This study also suggests a three-step mechanism of B-Z junction formation: (i) Zα specifically interacts with a CG-rich segment maintaining B-DNA via a unique conformation; (ii) the neighboring AT-rich region becomes very unstable, and the CG-rich segment is easily converted to Z-DNA; and (iii) the AT-rich regions are base-paired again, and the B-Z junction structure is formed. These results can explain how Zα protein specifically recognizes the alternating d(CG)n sequence in a long genomic B-DNA. We also performed NMR experiments on Z-DNA complexed with various mutant Zα proteins, which provide the information about role of each residue of Zα protein during B-Z transition. In addition, the systematic NMR study on the A-Z transition of RNA duplex induced by Zα and its comparison with B-Z transition of DNA provide insight into the biological function of Z-DNA binding protein during RNA-related proces.