Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics Journal Article
| Authors: | Patel, D. J.; Phan, A. T.; Kuryavyi, V. |
| Article Title: | Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: Diverse higher order DNA and RNA targets for cancer therapeutics |
| Abstract: | Guanine-rich DNA sequences can form G-quadruplexes stabilized by stacked G-G-G-G tetrads in monovalent cation-containing solution. The length and number of individual G-tracts and the length and sequence context of linker residues define the diverse topologies adopted by G-quadruplexes. The review highlights recent solution NMR-based G-quadruplex structures formed by the four-repeat human telomere in K+ solution and the guanine-rich strands of c-myc, c-kit and variant bcl-2 oncogenic promoters, as well as a bimolecular G-quadruplex that targets HIV-1 integrase. Such structure determinations have helped to identify unanticipated scaffolds such as interlocked G-quadruplexes, as well as novel topologies represented by double-chain-reversal and V-shaped loops, triads, mixed tetrads, adenine-mediated pentads and hexads and snap-back G-tetrad alignments. The review also highlights the recent identification of guanine-rich sequences positioned adjacent to translation start sites in 5′-untranslated regions (5′-UTRs) of RNA oncogenic sequences. The activity of the enzyme telomerase, which maintains telomere length, can be negatively regulated through G-quadruplex formation at telomeric ends. The review evaluates progress related to ongoing efforts to identify small molecule drugs that bind and stabilize distinct G-quadruplex scaffolds associated with telomeric and oncogenic sequences, and outlines progress towards identifying recognition principles based on several X-ray-based structures of ligand-G-quadruplex complexes. © 2007 The Author(s). |
| Keywords: | unclassified drug; oncoprotein; promoter region; sequence analysis; review; nonhuman; antineoplastic agent; neoplasms; telomere; gene targeting; imatinib; stem cell factor receptor; antineoplastic activity; enzyme activity; oncogenes; rna; oncogene; dna; double stranded dna; 5' untranslated region; daunorubicin; telomerase reverse transcriptase; dna structure; protein structure; dna determination; enzyme localization; human immunodeficiency virus 1; g-quadruplexes; rna sequence; 5' untranslated regions; promoter regions (genetics); 2.6 diamidodianthraquinone; 5,20, tetrakis n methyl 4 pyridyl; anthraquinone derivative; braco 19; guanosine phosphate; integrase inhibitor; monovalent cation; porphyrin; regulatory dna sequence; dna repeat expansion |
| Journal Title: | Nucleic Acids Research |
| Volume: | 35 |
| Issue: | 22 |
| ISSN: | 0305-1048 |
| Publisher: | Oxford University Press |
| Date Published: | 2007-12-01 |
| Start Page: | 7429 |
| End Page: | 7455 |
| Language: | English |
| DOI: | 10.1093/nar/gkm711 |
| PUBMED: | 17913750 |
| PROVIDER: | scopus |
| PMCID: | PMC2190718 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 196" - "Export Date: 17 November 2011" - "CODEN: NARHA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work