Unusual DNA conformations: implications for telomeres.
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 conformations. 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.
Mills
Martin
M
Laboratoire de Biophysique, INSERM U565 CNRS UMR 8646, Muséum National d'Histoire Naturelle, 75005 Paris, France.
Lacroix
Laurent
L
Arimondo
Paola B
PB
Leroy
Jean-Louis
JL
François
Jean-Christophe
JC
Klump
Horst
H
Mergny
Jean-Louis
JL
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016615:Telomere / Q000187:drug effects*
D000970:Antineoplastic Agents; D009841:Oligonucleotides; D004247:DNA