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Analytical Chemistry of Quadruplex DNA
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Raimundo Gargallo

Phone: 93 403 92 74
Fax: 93 402 12 33

 

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Current research activity

The name of our research area wants to synthesize in few words our activity. We are interested in the study of solution equilibria of complex structures of DNA and in the development of analytical methodology for their study. Nowadays, we are studying the solution equilibria of several DNA sequences corresponding to the oncogenes bcl-2, k-ras or c-kit. These genes contain guanine-cytosine-rich regions that are implicated in the regulation of the corresponding gene expression. In these regions, one of the strands of the DNA double helix is guanine-rich, and the other one is cytosine-rich.

The guanine-rich region can form complex structures known as G-quadruplex. The core of this structure is the tetrad of four guanine bases. G-quadruplexes show the formation of several tetrads from just one, two or four DNA strands. There is an increasing interest in the study of G-quadruplex because of their recent discovery in vivo and their possible role in biological processes like cancer.

G-quadruplex structure formed by three tetrads of four guanines each one (image from Wikipedia)

 
 
Although the guanine-rich strands is been widely studied, the complementary cytosine-rich strands have received little attention. Cytosine-rich DNA strands can form a cytosine+•cytosine tetraplex, known as i-motif, at low or even neutral pH. This structure consists of four strands arranged in two parallel duplexes “zipped” together in antiparallel orientation (see below). i-motif is the only known nucleic acid structure involving systematic base intercalation.

Recent interest has been shown in the study of i-motif structures due to their potential application in nanotechnology and their possible roles in gene transcription. Although low pH favors the formation of i-motif structures and they have not been reported in vivo, the sequences with the potential to form i-motifs are frequent in the human genome. To date, i-motif structures have been postulated in both centromeric and telomeric regions of human chromosomes, as well as in the promoter region of several genes.

For the study of solution equilibria involving G-quadruplex and i-motif structures we use molecular absorption, molecular fluorescence and circular dichroism spectroscopies, HPLC-DAD, and Surface Plasmon Resonance (SPR).

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layout image © Universitat de Barcelona Edition: R.Gargallo
Last update: 16.11.2009
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