Studies on effect of DNA tetraplex in gene regulation

Abstract

Since the discovery of DNA as a double helix molecule, many other non B-DNA forms of DNA are being uncovered. The investigators are interested in other forms of DNA which could potentially be formed in certain specialized regions of DNA. Various regions of DNA which are rich in purines (guanines) or pyrimidines (cytosine) can adopt folded four stranded structures called as G quadruplex and imotif respectively. Such sequences are known to be present at the telomeric ends of chromosomes, gene promoter regions, recombination sites, RNA dimerization domains and RNA packaging sites. Among all those, four stranded cytosine rich (tetraplex or i-motif) or guanine rich motif (Quadruplex or G4 DNA) have gained a lot of attention. The four stranded structure of these motifs is stabilized by a special kind of hydrogen bonding called hoogsteen bonding between two hemi-protonated cytosines, in case of tetraplex and between two guanines, in case of quadruplex structures. Tetraplex motif existence, inside the cells, has not been shown but there are in vitro evidences which support the possibility of their formation. Biological importance of tetraplex motifs has been shown in case of progressive myoclonus epilepsy, where multiple dodecamer cytosine repeats were shown to be involved in the disease. Also tetraplex formation is most favored in acidic conditions thus their existence inside cells is questionable. But certainly the complementary strand of potential i-motif forming sequence has the possibility to form a four stranded guanine rich quadruplex motifs. Various studies have implicated the role of quadruplex motifs in several biological phenomenons like transcription and recombination.