The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Formation of a Unique End-to-End Stacked Pair of G-Quadruplexes in the hTERT Core Promoter with Implications for Inhibition of Telomerase by G-Quadruplex-Interactive Ligands
Open accessAbstract
The hTERT core promoter contains a G-rich region of 12 consecutive G-tracts, embracing 3 Sp1 binding sites, and has the potential to form multiple G-quadruplexes. From the 12 runs of guanines, 9 putative hTERT G-quadruplex-forming sequences were selected to assay for G-quadruplex formation and stability using circular dichroism and a Taq polymerase stop assay. Results from biophysical and chemical assays demonstrate an approximate inverse correlation between total loop size and structure stability. Investigation of the full-length hTERT G-rich sequence using a Taq polymerase stop assay and dimethyl sulfate footprinting revealed the formation of a unique end-to-end stacked G-quadruplex structure from this sequence. This structure consists of an all parallel G-quadruplex, formed by four consecutive G-tracts, linked to another, atypical G-quadruplex, formed by two pairs of consecutive G-tracts separated by a 26-base loop. This 26-base loop likely forms a stable hairpin structure, which would explain the unexpected stability of this G-quadruplex. Significantly, the formation of this tandem G-quadruplex structure in the full-length sequence masks all three Sp1 binding sites, which is predicted to produce significant inhibition of hTERT promoter activity. Furthermore, our study implies that inhibition of telomerase activity by some G-quadruplex ligands is not only produced by targeting telomeric G-quadruplexes but also by stabilization of the hTERT promoter G-quadruplexes.
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Inhibition of Human Telomerase by a G-Quadruplex-Interactive Compound
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Telomestatin, a Novel Telomerase Inhibitor from Streptomyces anulatus
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Propeller-Type Parallel-Stranded G-Quadruplexes in the Human c-myc Promoter
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Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. D., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., et al. (2015) · Science · doi:10.1126/science.aab0015 · Cited by 566
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Brooks, T. A., Kendrick, S., & Hurley, L. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07759.x · Cited by 477
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Self-citationPont, A. R., Sadri, N., Hsiao, S. J., Smith, S., & Schneider, R. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.019 · Cited by 139
Metadata
- Authors
- Palumbo, S. L., Ebbinghaus, S. W., & Hurley, L. H.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-07-14
- Volume
- 131
- Issue
- 31
- Pages
- 10878-10891
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2022287291
- Cited by
- 279
- References
- 60
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- green
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