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