Z-DNA in the genome: from structure to disease

The scope of studies investigating the architecture of genomic DNA has progressed steadily since the elucidation of the structure of B-DNA. In recent years, several non-canonical DNA structures including Z-DNA, G-quadruplexes, H-DNA, cruciform DNA, and i-motifs have been reported to form in genomic DNA and are closely related to the evolution and development of disease. The ability of these structures to form in genomic DNA indicates that they might have important cellular roles and are therefore retained during evolution. Understanding the impact of the formation of these secondary structures on cellular processes can enable identification of new targets for therapeutics. In this review, we report the state of understanding of Z-DNA structure and formation and their implication in disease. Finally, we state our perspective on the potential of Z-DNA as a therapeutic target.