The new models of the human telomere DNA in K+ solution revealed by NMR analysis assisted by the incorporation of 8-bromoguanines.

Abstract

The structure of human telomeric DNA has been controversial: the solution structure in the presence of Na(+) has been reported to be antiparallel basket-type quadruplex by NMR, while the crystal structure in the presence of K(+) has been reported to be parallel propeller-type quadruplex. The solution structure in the presence of K(+) has drawn intense interest, as the intracellular K(+) concentration is higher than that of Na(+), but the structure is still open to address. Recently Sugiyama et al. has suggested that the DNA exists as a mixture of mixed-parallel/antiparallel quadruplex and antiparallel chair-type quadruplex on the basis of the combination of a series of 8-bromoguanine mutations and CD analysis. Here, we have started NMR analysis of the DNAs with the mutations to evaluate the proposed model. So far, NMR analysis is qualitatively consistent with the proposal. The structure determination is in progress to evaluate the model at atomic resolution.