Nucleic Acids Research Advance Access first published online on October 2, 2007
This version published online on November 17, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm711
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Survey and Summary |
Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA and 2Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore
*To whom correspondence should be addressed. Tel: +1 212 639 7207; Fax: +1 212 717 3066; Email: pateld{at}mskcc.org
Received July 25, 2007. Revised August 24, 2007. Accepted August 27, 2007.
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Arora, M. Dutkiewicz, V. Scaria, M. Hariharan, S. Maiti, and J. Kurreck Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif RNA, July 1, 2008; 14(7): 1290 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Gray and J. B. Chaires Kinetics and mechanism of K+- and Na+-induced folding of models of human telomeric DNA into G-quadruplex structures Nucleic Acids Res., July 1, 2008; 36(12): 4191 - 4203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Haider, G. N. Parkinson, and S. Neidle Molecular Dynamics and Principal Components Analysis of Human Telomeric Quadruplex Multimers Biophys. J., July 1, 2008; 95(1): 296 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-D. Beaudoin and J.-P. Perreault Potassium ions modulate a G-quadruplex-ribozyme's activity RNA, June 1, 2008; 14(6): 1018 - 1025. [Abstract] [Full Text] [PDF]
|
|