Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2007 Nov;8(11):1003-10.
doi: 10.1038/sj.embor.7401073. Epub 2007 Sep 28.

Quartets in G-major. The First International Meeting on Quadruplex DNA

Paula Bates  1 , Jean-Louis Mergny, Danzhou Yang
Affiliations
Review

Quartets in G-major. The First International Meeting on Quadruplex DNA

Paula Bates et al. EMBO Rep. 2007 Nov.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Paula Bates is a consultant and shareholder for Antisoma PLC (London, UK).

Figures

Figure 1
Figure 1
The quadruplex. (A) A tetrameric, dimeric and monomeric G-quadruplex composed of three G-quartets (top). (B) A schematic model of DNA secondary structure composed of compact-stacking multimers of the hybrid-type quadruplex structures (top and middle) in human telomeres. The model of the compact-stacking multimers of the parallel-stranded structures is also shown (bottom).
Figure 2
Figure 2
Quadruplex polymorphism. Examples of intramolecular G-quadruplexes with different folding and capping structures. Intramolecular G-quadruplex structures are all derived from a single-stranded DNA (top). The conformational diversity suggests that these G-quadruplex structures might be specifically recognized by various proteins and small molecule ligands. c-myc reprinted with permission from Ambrus et al (2005), copyright 2005 American Chemical Society; bcl-2 reprinted with permission from Dai et al (2006b); hTel-1 reprinted with permission from Dai et al (2007b); hTel-2 reprinted with permission from Dai et al (2007a).
Figure 3
Figure 3
Quadruplex in a gene promoter. Alternative forms of the NHE III1 of the c-myc promoter associated with transcriptional activation or silencing. CNBP, cellular nucleic acid binding protein; hnRNP, heterogeneous nuclear ribonucleoprotein; NHE III, nuclease hypersensitive element III; TBP, TATA binding protein.
Figure 4
Figure 4
Quadruplexes in biology and as therapeutic agents or targets. Cartoon illustrating some possible roles of quadruplex formation in vivo and therapeutic strategies based on quadruplex formation. Antiparallel quadruplexes are shown for simplicity, but actual structures might vary. (A) Quadruplex formation in the single-stranded regions of telomeres. Ligands that stabilize the quadruplex might lead to cellular senescence by preventing telomere extension mediated by telomerase (TEL), and might also induce rapid apoptosis by displacing telomere-binding proteins, for example, protection of telomeres 1 (POT1). (B) Quadruplex formation in the context of duplex DNA is now suspected for many gene promoter regions, especially oncogene promoters. The quadruplex structure is a transcriptional repressor for some oncogenes, for example, c-MYC, and quadruplex-stabilizing ligands might act to block transcription. (C) Quadruplexes can also form in RNA and might hinder translation. (D) Ribosomal genes (rDNA), which are located in the nucleolus of the cell, contain a high concentration of potential quadruplex-forming sequences. These rDNA quadruplexes seem to be the target of CX-3543, a quadruplex-binding small molecule that is now in clinical trials as an anticancer agent. CX-3543 localizes to nucleoli and prevents nucleolin protein (NCL) from binding to rDNA quadruplexes, leading to inhibition of ribosome biogenesis. (E) AS1411 is a quadruplex-forming oligonucleotide that is now being tested in human clinical trials. This molecule also targets nucleolin protein and seems to bind to the cell surface form of the protein, which is present at high levels in cancer cells, leading to internalization of the complex. AS1411 can affect the molecular interactions and transport of nucleolin, thereby inhibiting many cancer cell survival pathways.
None
Jean-Louis Mergny, Paula Bates & Danzhou Yang
None
The First International Meeting on Quadruplex DNA took place between 21 and 24 April 2007, in Louisville, Kentucky, USA. The meeting followed two regional workshops (pan-Pacific and European) in Hawai (2005) and Slovenia (2006), and was organized by J. Chaires and L. Hurley.
See this image and copyright information in PMC

References

    1. Alberti P, Bourdoncle A, Saccà B, Lacroix L, Mergny JL (2006) DNA nanomachines and nanostructures involving quadruplexes. Org Biomol Chem 4: 3383–3391 - PubMed
    1. Ambrus A, Chen D, Dai J, Jones RA, Yang D (2005) Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. implications for G-quadruplex stabilization. Biochem 44: 2048–2048 - PubMed
    1. Ambrus A, Chen D, Dai J, Bialis T, Jones RA, Yang D (2006) Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res 34: 2723–2735 - PMC - PubMed
    1. Dai JX, Dexheimer TS, Chen D, Carver M, Ambrus A, Jones RA, Yang DZ (2006a) An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution. J Am Chem Soc 128: 1096–1098 - PMC - PubMed
    1. Dai J, Chen D, Jones RA, Hurley LH, Yang D (2006b) NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nuc Acid Res 34: 5133–5144 - PMC - PubMed