Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter Journal Article
| Authors: | Kuryavyi, V.; Phan, A. T.; Patel, D. J. |
| Article Title: | Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter |
| Abstract: | Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K+-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K+-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K+-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3′ to 5′-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex. © The Author(s) 2010. Published by Oxford University Press. |
| Keywords: | unclassified drug; promoter region; protein conformation; stem cell factor receptor; proto-oncogene proteins c-kit; amino acid sequence; guanine; promoter regions, genetic; models, molecular; protons; dimerization; protein structure; chromosome pairing; synapsis; g-quadruplexes; guanine quadruplex; nuclear magnetic resonance, biomolecular; circular dichroism; potassium ion; stem cell factor receptor 2 |
| Journal Title: | Nucleic Acids Research |
| Volume: | 38 |
| Issue: | 19 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2010-10-01 |
| Start Page: | 6757 |
| End Page: | 6773 |
| Language: | English |
| DOI: | 10.1093/nar/gkq558 |
| PUBMED: | 20566478 |
| PROVIDER: | scopus |
| PMCID: | PMC2965254 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "Art. No.: gkq558" - "CODEN: NARHA" - "Source: Scopus" |
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