Structural and thermodynamic studies of a DNA i-motif: Investigating the monomer, dimer, and tetramer human telomere sequence context




McKim, Mikeal

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Telomeres are protein DNA complexes found at the ends of eukaryotic chromosomes. The human telomere sequence has a G-rich strand, (TTAGGG), complemented to a C-rich strand, (CCCTAA). Previous studies of the G-rich strand indicate that this sequence folds into a distinct conformation, designated as a G quadruplex. The C-rich strand has also been shown to form an unusual structure, under slightly acidic conditions, designated as a DNA i-motif. We are investigating the role of the loops on the structure and stability of the conformations formed from (CCCXXX)4, where X is all permutations of A and/or T. To understand the significance of the presence of the loops, structure and stability will be studied for the dimer and tetramer conformations formed from (CCCTAA)x, where X is either a 1 or a 2. These results indicate that the sequence context and the presence or absence of the loops, influences both the midpoint of the heat induced i-motif to single strand transition (Tm) at pH = 5.0, as well as, the midpoint of the H + induced single strand to i-motif transition (pHmp) at 25 °C.



Pure sciences, Biological sciences, Cytosine, DNA, Enthalpy, Entropy, I-motif, Protonation