The Crystal Structure of a Junction Between Two Z-DNA Helices
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de Rosa-2010-Crystal structure of.pdf
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Author(s)
Rich, Alexander
de Rosa, Matteo
de Sanctis, Daniele
Rosario, Ana Lucia
Archer, Margarida
Athanasiadis, Alekos
Carrondo, Maria Armenia
Date Issued
May 2010
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
De Rosa, Matteo, et al. "Crystal structure of a junction between two Z-DNA helices." PNAS May 18, 2010 vol. 107 no. 20 9088-9092. ©2010 by the National Academy of Sciences.
Version
Final published version
Abstract
The double helix of DNA, when composed of dinucleotide purine-pyrimidine repeats, can adopt a left-handed helical structure called Z-DNA. For reasons not entirely understood, such dinucleotide repeats in genomic sequences have been associated with genomic instability leading to cancer. Adoption of the left-handed conformation results in the formation of conformational junctions: A B-to-Z junction is formed at the boundaries of the helix, whereas a Z-to-Z junction is commonly formed in sequences where the dinucleotide repeat is interrupted by single base insertions or deletions that bring neighboring helices out of phase. B-Z junctions are shown to result in exposed nucleotides vulnerable to chemical or enzymatic modification. Here we describe the three-dimensional structure of a Z-Z junction stabilized by Zα, the Z-DNA binding domain of the RNA editing enzyme ADAR1. We show that the junction structure consists of a single base pair and leads to partial or full disruption of the helical stacking. The junction region allows intercalating agents to insert themselves into the left-handed helix, which is otherwise resistant to intercalation. However, unlike a B-Z junction, in this structure the bases are not fully extruded, and the stacking between the two left-handed helices is not continuous.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1073/pnas.1003182107
