The crystal structure of BZ-junction reveals that left-handed Z-DNA stabilized by Z-DNA binding domain (Zα) is continuously stacked to right-handed B-DNA with AT bases' extrusion in the junction site. Show more
The crystal structure of BZ-junction reveals that left-handed Z-DNA stabilized by Z-DNA binding domain (Zα) is continuously stacked to right-handed B-DNA with AT bases' extrusion in the junction site. However, this structure might not fully represent the BZ-junction in solution due to the possibility of the junction formation either by crystal packing or Zα interaction. Therefore, we investigated BZ-junction in solution with chemical Z-DNA inducers using CD and 2-aminopurine base-extrusion assay. We confirmed the formation of Z-DNA and BZ-junction with base-extrusion by chemical Z-DNA inducers. However, neither typical Z-DNA nor base-extrusion could be detected with some inducers such as spermine, suggesting that the energy barrier for the formation of the BZ junction might vary depending on the Z-DNA induction conditions. Show less
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 includ Show more
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. Show less
Left-handed Z-DNA/Z-RNA is bound with high affinity by the Zα domain protein family that includes ADAR (a double-stranded RNA editing enzyme), ZBP1 and viral orthologs regulating innate immunity. Loss Show more
Left-handed Z-DNA/Z-RNA is bound with high affinity by the Zα domain protein family that includes ADAR (a double-stranded RNA editing enzyme), ZBP1 and viral orthologs regulating innate immunity. Loss-of-function mutations in ADAR p150 allow persistent activation of the interferon system by Alu dsRNAs and are causal for Aicardi-Goutières Syndrome. Heterodimers of ADAR and DICER1 regulate the switch from RNA- to protein-centric immunity. Loss of DICER1 function produces age-related macular degeneration, a different type of Alu-mediated disease. The overlap of Z-forming sites with those for the signal recognition particle likely limits invasion of primate genomes by Alu retrotransposons. Show less