Unveiling the pathway to Z-DNA in the protein-induced B-Z transition

Sook Ho Kim, So Hee Lim, Ae Ree Lee, Do Hoon Kwon, Hyun Kyu Song, Joon Hwa Lee, Minhaeng Cho, Albert Johner, Nam Kyung Lee, Seok Cheol Hong

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences. We also reported what pathways it takes to induce the B-Z transition in those sequences. Due to the high junction energy, an intermediate B state has to accumulate prior to the B-Z transition. Our study showing the stable B state supports the active picture for the protein-induced B-Z transition that occurs under a physiological setting.

Original languageEnglish
Pages (from-to)4129-4137
Number of pages9
JournalNucleic acids research
Volume46
Issue number8
DOIs
Publication statusPublished - 2018 May 4

Bibliographical note

Funding Information:
National Research Foundation of Korea [NRF-2014R1A1A2055681 and NRF-2017R1A2B4010632 to N.-K.L., NRF-2016R1A2B4014855 to S.-C.H.]: Institute for Basic Science [IBS-R023-D1 to S.-C.H.]. Funding for open access charge: Institute for Basic Science [IBS-R023-D1]. Conflict of interest statement. None declared.

Publisher Copyright:
© The Author(s) 2018.

ASJC Scopus subject areas

  • Genetics

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