Biophysical interaction between lanthanum chloride and (CG)_n or (GC)_n 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)_n and (GC)_n 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)₆ DNA using millimolar concentration of trivalent lanthanide salt LaCl₃. The controlled and reversible transition was seen in (CG)₁₂, and (GC)₁₂ DNA employing CD spectroscopy. While LaCl₃ failed to induce B-Z transition in shorter oligonucleotides such as (CG)₃ and (GC)₃, a smooth B-Z transition was recorded for (CG)₆, (CG)₁₂ and (GC)₁₂ 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)₆ DNA in presence of LaCl₃ 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 LaCl₃-induced Z-DNA is irreversible which suggest a stronger binding of LaCl₃ 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 La³⁺ (of LaCl₃) with d(CG)₈.d(CG)₈ is through the minor groove, wherein, 3 out of 11 La³⁺ bridge the anionic oxygens of the complementary strands. Such a tight coordination of La³⁺ with the anionic oxygens at the minor groove surface may be the reason for the experimentally observed irreversibility of LaCl₃-induced Z-DNA seen in longer DNA fragments. Thus, these results indicate LaCl₃ 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.