Unusual DNA Conformations: Implications for Telomeres

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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5 - Year: 2.849

Unusual DNA Conformations: Implications for Telomeres



Anti-Cancer Agents in Medicinal Chemistry, 2(5): 627-644.

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

Affiliation: Laboratoire de Biophysique,INSERM U565 CNRS UMR 8646, Museum National d'Histoire Naturelle,75005 Paris, France

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 Number: 5
First Page: 627
Last Page: 644
Page Count: 18
DOI: 10.2174/1568011023353877
Price: $58
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