Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6493617 | Journal of Photochemistry and Photobiology B: Biology | 2016 | 8 Pages |
Abstract
C-myb proto-oncogene is a potential therapeutic target for some human solid tumors and leukemias. A long cytosine-rich sequence, which locates the downstream of the transcription initiation site, is demonstrated to fold into an intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the pH value, the number of C:C+ dimers, the concentration of buffer, the molecular crowding condition, and the coexistence of the complementary DNA, on the formation and the structural stability of the i-motif DNA are systematically studied. We have demonstrated that the i-motif folding in the c-myb promoter could be accelerated upon synergistic physiological stimuli including intracellular molecular crowding and low pH values, as well as the large number of the i-motif C:C+ dimers. Meanwhile, various inputs, such as acids/bases and metal ions, have exhibited their abilities in controlling the conformational switch of the c-myb GC-rich DNA. Acidic pH values and the presence of K+ ions can induce the dissociation of the double helix. Our present strategy can greatly extend the potential usages of i-motif DNA molecules with specific sequences as conformational switch-controlled devices. Moreover, this work demonstrates the superiority of CD spectroscopy associated with ESI-MS as a rapid, more cost-effective and sensitive structural change responsive method in the research of DNA conformational switching.
Keywords
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
Huihui Li, Jinhui Hai, Jiang Zhou, Gu Yuan,