STRUCTURES OF DNA AND RNA QUADRUPLEXES

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Purine-rich nucleotide sequences have been implicated in a number of important biological processes. These include roles in eucaryotic chromosome replication, gene regulation, meiosis and the retrovirus replication cycle. Over the past several years it has become clear that at least some of these functions are intimately connected with the ability for purine-rich oligonucleotides to form quadruplex structures that are stabilized by G-quartets. In the work proposed here, NMR spectroscopy will be used to determine the high resolution solution structures of several DNA and RNA oligonucleotides which are known, or suspected to, form G-quartets under physiological conditions. The oligonucleotides selected for study are intended to answer specific questions related the higher order structures of DNA and RNA sequences found in telomeres and retrovirus genomes, respectively. The long term goals of the DNA studies are to understand the normal functionality of telomeres in chromosome replication and cell division. The RNA studies are directed towards an increased understanding of the retrovirus replication cycle and identification of promising targets for anti-viral agents.