A topological transition from bimolecular quadruplex to G-triplex/tri-G-quadruplex exhibited by truncated double repeats of human telomere.

Human telomeric G-rich sequences can fold back into various conformations depending upon the salt (Na or K) at physiological pH. On the basis of results obtained by native PAGE electrophoresis, circular dichroism, and UV-melting experiments, we report here that truncated sequences of human telomere (d-GGGTTAGGG; GM9, d-AGGGTTAGGG; GM10, d-TAGGGTTAGGG; GM11) adopt a varied range of quadruplex conformations as a function of the cation present. By correlating CD and gel electrophoresis experiments; it was concluded that the GM9 oligonucleotide can self-associate to form a tetramer quadruplex (antiparallel; AP) in Na solution and a mixture of G-triplex (AP) or tri-G-quadruplex (parallel; P) along with a tetramer G-quadruplex structure (AP) in K. The GM10 oligonucleotide formed a bimolecular G-quadruplex in both Na and K solutions, while GM11 associated to form a bimolecular G-quadruplex (AP) structure in Na solution and a mixture of bimolecular G-quadruplex (AP) and bimolecular G-quadruplex (P) along with parallel G-triplex or antiparallel tri-G-quadruplex in K. All the UV-melting profiles, thermal difference spectra, and CD melting curves suggested the formation of a variety of G-quadruplex conformations by the DNA sequences studied in Na and K ions. Hypothetical models for different conformations adopted by these DNA molecules have also been proposed, which may further enhance our knowledge about the divergent topologies of guanine quadruplexes.