Nucleic Acids Research, Vol 26, Issue 15 3486-3493, Copyright © 1998 by Oxford University Press
A Herbert, M Schade, K Lowenhaupt, J Alfken, T Schwartz, LS Shlyakhtenko, YL Lyubchenko and A Rich
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,
Zalpha and Zbeta, the function of which is currently unknown. Here we show
that a peptide containing the Zalpha motif binds with high affinity to
Z-DNA as a dimer, that the binding site is no larger than 6 bp and that the
Zalpha domain can flip a range of sequences, including d(TA)3, into the
Z-DNAconformation. Evidence is also presented to show that Zalpha and Zbeta
interact to form a functional DNA binding site. Studies with atomic force
microscopy reveal that binding of Zalpha to supercoiled plasmids is
associated with relaxation of the plasmid. Pronounced kinking of DNA is
observed, and appears to be induced by binding of Zalpha. 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 Zalpha would be dependent upon the local level of
negative superhelicity rather than the presence of any particular sequence.
ARTICLES
The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences
Department of Biology Room 68-233, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. alan@mit.edu
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