Single-molecule analysis of i-motif within self-assembled DNA duplexes and nanocircles
| العنوان: | Single-molecule analysis of i-motif within self-assembled DNA duplexes and nanocircles |
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| المؤلفون: | Peter D Wilkerson, Kumar Sapkota, Anoja Megalathan, Joseph E. Reiner, Anisa Kaur, Bobby D. Cox, Soma Dhakal |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Models, Molecular, Circular dichroism, Kinetics, Biology, 010402 general chemistry, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Cytosine, Nanopores, Chemical Biology and Nucleic Acid Chemistry, Genetics, Molecule, Humans, Nucleotide Motifs, 030304 developmental biology, 0303 health sciences, Oligonucleotide, Circular Dichroism, DNA, Hydrogen-Ion Concentration, 0104 chemical sciences, genomic DNA, Nanopore, chemistry, Microscopy, Fluorescence, Biophysics, Nucleic Acid Conformation, Algorithms |
| الوصف: | The cytosine (C)-rich sequences that can fold into tetraplex structures known as i-motif are prevalent in genomic DNA. Recent studies of i-motif–forming sequences have shown increasing evidence of their roles in gene regulation. However, most of these studies have been performed in short single-stranded oligonucleotides, far from the intracellular environment. In cells, i-motif–forming sequences are flanked by DNA duplexes and packed in the genome. Therefore, exploring the conformational dynamics and kinetics of i-motif under such topologically constrained environments is highly relevant in predicting their biological roles. Using single-molecule fluorescence analysis of self-assembled DNA duplexes and nanocircles, we show that the topological environments play a key role on i-motif stability and dynamics. While the human telomere sequence (C3TAA)3C3 assumes i-motif structure at pH 5.5 regardless of topological constraint, it undergoes conformational dynamics among unfolded, partially folded and fully folded states at pH 6.5. The lifetimes of i-motif and the partially folded state at pH 6.5 were determined to be 6 ± 2 and 31 ± 11 s, respectively. Consistent with the partially folded state observed in fluorescence analysis, interrogation of current versus time traces obtained from nanopore analysis at pH 6.5 shows long-lived shallow blockades with a mean lifetime of 25 ± 6 s. Such lifetimes are sufficient for the i-motif and partially folded states to interact with proteins to modulate cellular processes. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12b24fd64a4036f18167585952467725 http://europepmc.org/articles/PMC6698746 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....12b24fd64a4036f18167585952467725 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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