Current Medicinal Chemistry - Anti-Cancer Agents

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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Unusual DNA Conformations: Implications for Telomeres

Author(s): Martin Mills, Laurent Lacroix, Paola B. Arimondo, Jean-Louis Leroy, Jean-Christophe Francois, Horst Klump, Jean-Louis Mergny.

Abstract:

DNA is prone to structural polymorphism: its three-dimensional structure can differ markedly from the classical double helix. Nucleic acid structures composed of more than two strands have also been observed. The guanine-rich sequence of both the telomere and centromere can form a quadruplex based on G-quartets while the complementary cytosine-rich strand can fold into an intercalated tetramer called the i-motif. The G-quartet is a gold mine for structural biologists and the telomere has become a target for anti-cancer drug design since it was observed that deregulation of telomerase favors proliferation of certain tumors. Other DNA sequences may adopt unusual confor-mations. Polypurine-polypyrimidine sequences capable of forming a triple-stranded structure called H-DNA are found abundantly in the eukaryotic genome and may play a significant role in DNA metabolism, transcription and replication. Triplex-forming oligonucleotides are currently being developed as “anti-gene” agents. Unusual DNA structures may therefore be implicated in fundamental processes such as gene expression and represent unique targets for both structural-specific and sequence-specific agents. In this review, we present work characterizing some of these unusual conformations in terms of structure, stability and formation kinetics and discuss their biological implications.

Keywords: Telomeres, i-motif, Guanine Quadruplexes

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Article Details

VOLUME: 2
ISSUE: 5
Year: 2002
Page: [627 - 644]
Pages: 18
DOI: 10.2174/1568011023353877
Price: $58