title: Novel interaction of the Z-DNA binding domain of human ADAR1 with the oncogenic c-Myc promoter G-quadruplex.
abstract: Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Tuong Vy Thi
authors.initials: TV
authors.lastname: Le
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Jeonghwan
authors.initials: J
authors.lastname: Hur
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Kyeong Kyu
authors.initials: KK
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D043542:DNA, Z-Form / Q000378:metabolism*; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins
chemical_list: D043542:DNA, Z-Form; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
keywords: Z-DNA binding domain of human ADAR1; c-Myc G-quadruplex