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.
Crystal structure of a junction between two Z-DNA helices / M. de Rosa, D. de Sanctis, A.L. Rosario, M. Archer, A. Rich, A. Athanasiadis, M.A. Carrondo. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 107:20(2010), pp. 9088-9092.
|Titolo:||Crystal structure of a junction between two Z-DNA helices|
DE ROSA, MATTEO (Primo)
|Parole Chiave:||Base stacking; DNA structure; Extruded base; X-ray diffraction|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.1003182107|
|Appare nelle tipologie:||01 - Articolo su periodico|