NMR studies on truncated sequences of human telomeric DNA: observation of a novel A-tetrad

Abstract

The structure of the telomeric DNA has been a subject of extensive investigation in recent years due to the realization that it has important functional roles to play in vivo and the observations that truncated telomeric sequences exhibit a great variety of 3D structures in aqueous solutions. In this context, we describe here NMR structural studies on two truncated human telomeric DNA sequences, d-AG₃T and d-TAG₃T in solutions containing K⁺ ions. The G₃ stretches in both the oligonucleotides were seen to form parallel-stranded quadruplexes. However, the AG₃ segment as a whole, had different structural characteristics. The structure of d-AG₃T revealed the formation of a novel A-tetrad, which was not seen in d-TAG₃T. The A's in the tetrad had syn glycosidic conformation as opposed to the anti conformation of the G's in the G-tetrads. The A-tetrad stacked well over the adjacent G-tetrad and the twist angle at this step was smaller in d-AG₃T than in d-TAG₃T. These observations are expected to be significant from the point of view of structural diversity and recognition in telomeres.