Novel Interaction of the Z-DNA Binding Domain of Human ADAR1 with the Oncogenic c-Myc Promoter G-Quadruplex

作者：Kang Hyun Jin; Tuong Vy Thi Le; Kim Kyungmin; Hur Jeonghwan; Kim Kyeong Kyu; Park Hyun Ju^*

来源：Journal of Molecular Biology, 2014, 426(14): 2594-2604.

DOI：10.1016/j.jmb.2014.05.001

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 (hZ alpha(ADAR1)) 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 hZ alpha(ADAR1) to the intramolecular c-nnyc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZ alpha(ADAR1) to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZ alpha(ADAR1) 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 hZ alpha(ADAR1) was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZ alpha(ADAR1) 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.

• 出版日期2014-7-15