The Zα domain from human ADAR1 binds to the Z-DNA conformer of many different sequences

Alan Herbert, Markus Schade, Ky Lowenhaupt, Jens Alfken, Thomas Schwartz, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, Alexander Rich

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Z-DNA, the left-handed conformer of DNA, is stabilized by the negative supercoiling generated during the movement of an RNA polymerase through a gene. Recently, we have shown that the editing enzyme ADAR1 (double-stranded RNA adenosine deaminase, type 1) has two Z-DNA binding motifs, Zα and Zβ, the function of which is currently unknown. Here we show that a peptide containing the Zα motif binds with high affinity to Z-DNA as a dimer, that the binding site is no larger than 6 bp and that the Zα domain can flip a range of sequences, including d(TA)3, into the Z-DNA conformation. Evidence is also presented to show that Zα and Zβ interact to form a functional DNA binding site. Studies with atomic force microscopy reveal that binding of Zα to supercoiled plasmids is associated with relaxation of the plasmid. Pronounced kinking of DNA is observed, and appears to be induced by binding of Zα. The results reported here support a model where the Z-DNA binding motifs target ADAR1 to regions of negative supercoiling in actively transcribing genes. In this situation, binding by Zα would be dependent upon the local level of negative superhelicity rather than the presence of any particular sequence.

Original languageEnglish (US)
Pages (from-to)3486-3493
Number of pages8
JournalNucleic acids research
Volume26
Issue number15
DOIs
StatePublished - Aug 1 1998

    Fingerprint

ASJC Scopus subject areas

  • Genetics

Cite this

Herbert, A., Schade, M., Lowenhaupt, K., Alfken, J., Schwartz, T., Shlyakhtenko, L. S., Lyubchenko, Y. L., & Rich, A. (1998). The Zα domain from human ADAR1 binds to the Z-DNA conformer of many different sequences. Nucleic acids research, 26(15), 3486-3493. https://doi.org/10.1093/nar/26.15.3486