Biophysical interaction between lanthanum chloride and (CG) or (GC) repeats: A reversible B-to-Z DNA transition.

The transition from right-handed to left-handed DNA is not only acts as the controlling factor for switching gene expression but also has equal importance in designing nanomechanical devices. The (CG) and (GC) repeat sequences are well known model molecules to study B-Z transition in the presence of higher concentration of monovalent cations. In this communication, we report a cyclic transition in (CG) DNA using millimolar concentration of trivalent lanthanide salt LaCl. The controlled and reversible transition was seen in (CG), and (GC) DNA employing CD spectroscopy. While LaCl failed to induce B-Z transition in shorter oligonucleotides such as (CG) and (GC), a smooth B-Z transition was recorded for (CG), (CG) and (GC) sequences. Interestingly, the phenomenon was reversible (Z-B transition) with addition of EDTA. Particularly, two rounds of cyclic transition (B-Z-B-Z-B) have been noticed in (CG) DNA in presence of LaCl and EDTA which strongly suggest that B-Z transition is reversible in short repeat sequences. Thermal melting and annealing behaviour of B-DNA are reversible while the thermal melting of LaCl-induced Z-DNA is irreversible which suggest a stronger binding of LaCl to the phosphate backbone of Z-DNA. This was further supported by isothermal titration calorimetric study. Molecular dynamics (MD) simulation indicates that the mode of binding of La (of LaCl) with d(CG).d(CG) is through the minor groove, wherein, 3 out of 11 La bridge the anionic oxygens of the complementary strands. Such a tight coordination of La with the anionic oxygens at the minor groove surface may be the reason for the experimentally observed irreversibility of LaCl-induced Z-DNA seen in longer DNA fragments. Thus, these results indicate LaCl can easily be adopted as an inducer of left-handed DNA in other short oligonucleotides sequences to facilitate the understanding of the molecular mechanism of B-Z transition.