A single base permutation in any loop of a folded intramolecular quadruplex influences its structure and stability

Dinesh Yadav, Richard D. Sheardy

Department of Biology, Texas Woman’s University, Denton, USA.
Department of Chemistry and Biochemistry, Texas Woman’s University, Denton, USA.

DOI: 10.4236/jbpc.2012.34042                

Abstract

The human telomere sequence (TTAGGG)₄ folds into an unusual conformation possessing three G-tetrads linked by TTA loops. The first loop is a propeller loop while the second and third loops are transverse loops. Using Circular Dichroism (CD) spectroscopy, we have investigated the effect of sequence context on the structures and stabilities of intramolecular G-quadruplexes related to the human telomere sequence by considering all permutations of T and A within the loops. The results indicate that changing only one base in any one loop can have a dramatic effect on the conformation of the quadruplex as well as its melting temperature, T_m. Thus, each sequence studied has a unique CD spectrum and T_m. In general, variants with a modified second loop are the most stable while the wild type sequence is the least stable. The observed difference in CD spectra and melting temperature are discussed in terms of base stacking within the loop and stacking of the loop bases with adjacent G-tetrads.

Keywords

Cell DNA Quadruplexes; Sequence Context; Circular Dichroism; Structure; Stability

Conflicts of Interest

The authors declare no conflicts of interest.

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