Article ID Journal Published Year Pages File Type
1979387 Current Opinion in Structural Biology 2009 12 Pages PDF
Abstract

Quadruplex nucleic acids are four-stranded structures formed from short tracts of G-rich sequence associating together. Their formation from eukaryotic telomeric DNA sequences is well established, at least in vitro, and has more recently been the focus of attention as novel anticancer targets since their formation inhibits the telomerase complex from maintaining telomere length in cancer cells. Structural studies have revealed a diversity of topologies for telomeric quadruplexes, which are sensitive to the nature of the cations present, to the flanking sequences, and probably also to concentration. The small number of structures determined for ligand–quadruplex complexes have to date shown a marked preference for the quadruplex component to have all strands in a parallel folding arrangement, which maximises the planar surface available for ligand binding. Informatics has revealed that there are a large number of quadruplex sequences present in human and other genomes, both eukaryotic and prokaryotic, with over-representation in upstream promoter regions. Structures for a few of these are now available, which emphasise the role played by loop sequences in determining fold.

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