title: Crystal structure of a junction between two Z-DNA helices.
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 Zalpha, 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.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6 P-2780-156 Oeiras, Portugal.
authors.forename: Matteo
authors.initials: M
authors.lastname: de Rosa
authors.forename: Daniele
authors.initials: D
authors.lastname: de Sanctis
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Rosario
authors.forename: Margarida
authors.initials: M
authors.lastname: Archer
authors.forename: Alexander
authors.initials: A
authors.lastname: Rich
authors.forename: Alekos
authors.initials: A
authors.lastname: Athanasiadis
authors.forename: Maria Armenia
authors.initials: MA
authors.lastname: Carrondo
mesh_terms: D019295:Computational Biology; D003460:Crystallization; D043542:DNA, Z-Form / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014961:X-Ray Diffraction
chemical_list: D043542:DNA, Z-Form