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

Bhanjadeo, Madhabi M. and Nial, Partha S. and Sathyaseelan, Chakkarai and Singh, Ajit K. and Dutta, Juhi and Rathinavelan, Thenmalarchelvi and et al, . (2022) Biophysical interaction between lanthanum chloride and (CG)n or (GC)n repeats: A reversible B-to-Z DNA transition. International Journal of Biological Macromolecules, 216. pp. 698-709. ISSN 0141-8130

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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. © 2022 Elsevier B.V.

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IITH Creators:
IITH CreatorsORCiD
Rathinavelan, Thenmalarchelvi
Item Type: Article
Additional Information: This work was funded by the Council of Scientific and Industrial Research, Government of India to U.S. and 12th Five year plan project (ESC-401). The authors thank Dr Himansu S. Biswal and CIS Department of NISER, Bhubaneswar for helping to carry out the FTIR experiments. This manuscript is dedicated to Professor Alexander Rich in memory of his 98th Birth Anniversary.
Uncontrolled Keywords: B-Z transition; CG repeat; GC repeat; Lanthanum; Molecular dynamics simulation; Z-DNA
Subjects: Others > Nanotechnology
Others > Biotechnology
Others > Chemical sciences
Divisions: Department of Biotechnology
Depositing User: . LibTrainee 2021
Date Deposited: 21 Jul 2022 11:25
Last Modified: 21 Jul 2022 11:25
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