التفاصيل البيبلوغرافية
| العنوان: |
Novel Interaction of the Z-DNA Binding Domain of Human ADAR1 with the Oncogenic c-Myc Promoter G-Quadruplex. |
| المؤلفون: |
Kang, Hyun-Jin1, Le, Tuong Vy Thi1, Kim, Kyungmin2, Hur, Jeonghwan2, Kim, Kyeong Kyu2, Park, Hyun-Ju1 |
| المصدر: |
Journal of Molecular Biology. Jul2014, Vol. 426 Issue 14, p2594-2604. 11p. |
| مصطلحات موضوعية: |
*Z-DNA, *DNA-binding proteins, *HUMAN proteins, *MYC oncogenes, *PROMOTERS (Genetics), *QUADRUPLEX nucleic acids, *REPEATED sequence (Genetics), *GENE expression |
| مستخلص: |
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. [Copyright &y& Elsevier] |
| قاعدة البيانات: |
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