Characterization of the Structural Conformation Adopted by (TTAGGG)_n Telomeric DNA Repeats of Different Length in Closed Circular DNA

Abstract

Telomeric DNA sequences are known to adopt unusual DNA structures upon protonation when contained into negatively supercoiled DNA. In this paper, the structural properties of (T₂AG₃)_n telomeric sequences of different length is analyzed in detail. Transition to the protonated form is observed at very low pH for (T₂AG₃)_n<8 sequences. Formation of the protonated form is facilitated by negative supercoiling. The patterns of chemical modification obtained with different chemical reagents indicate that protonation induces denaturation of the (T₂AG₃)_n telomeric sequences. Upon denaturation, the “C-rich” strand becomes structured forming, most likely, hairpin-like conformations stabilized by the formation of C⁺·C pairs and, probably, of A⁺·A pairs. The “G-rich” strand of the (T₂AG₃)₈ sequence shows also signs of becoming structured giving rise to various structural conformers which might include triple- and tetra-stranded conformations. However, in the case of shorter sequences, the “G-rich” strand remains basically single-stranded.