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 LaCl ₃ . The controlled and reversible transition was seen in (CG) ₁₂ , and (GC) ₁₂ DNA employing CD spectroscopy. While LaCl ₃ 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 LaCl ₃ 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 ₃ -induced Z-DNA is irreversible which suggest a stronger binding of LaCl ₃ 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 ³⁺ (of LaCl ₃ ) with d(CG) ₈ .d(CG) ₈ is through the minor groove, wherein, 3 out of 11 La ³⁺ bridge the anionic oxygens of the complementary strands. Such a tight coordination of La ³⁺ with the anionic oxygens at the minor groove surface may be the reason for the experimentally observed irreversibility of LaCl ₃ -induced Z-DNA seen in longer DNA fragments. Thus, these results indicate LaCl ₃ 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.
(Copyright © 2022 Elsevier B.V. All rights reserved.)