Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases

  title={Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases},
  author={Sung Chul Ha and Ky Lowenhaupt and Alexander Rich and Yang‐Gyun Kim and Kyeong Kyu Kim},
Left-handed Z-DNA is a higher-energy form of the double helix, stabilized by negative supercoiling generated by transcription or unwrapping nucleosomes. Regions near the transcription start site frequently contain sequence motifs favourable for forming Z-DNA, and formation of Z-DNA near the promoter region stimulates transcription. Z-DNA is also stabilized by specific protein binding; several proteins have been identified with low nanomolar binding constants. Z-DNA occurs in a dynamic state… 
Crystal structure of a junction between two Z-DNA helices
The three-dimensional structure of a Z-Z junction stabilized by Zα, the Z-DNA binding domain of the RNA editing enzyme ADAR1, is described and it is shown that the junction structure consists of a single base pair and leads to partial or full disruption of the helical stacking.
NMR study on the B-Z junction formation of DNA duplexes induced by Z-DNA binding domain of human ADAR1.
The findings suggest a three-step mechanism of B-Z junction formation: (i) Zα(ADAR1) specifically interacts with a CG-rich DNA segment maintaining B-form helix via a unique conformation; (ii) the neighboring AT-rich region becomes very unstable, and the CG- rich DNA segment is easily converted to Z-DNA.
Intrinsic Z-DNA is stabilized by the conformational selection mechanism of Z-DNA-binding proteins.
The results reveal that intrinsic Z-DNAs are dynamically formed and effectively stabilized by Z-DNA-binding proteins through efficient trapping of the Z conformation rather than being actively induced by them.
Sequence-specific B-DNA flexibility modulates Z-DNA formation.
It is shown that sequence-specific B-DNA flexibility modulates the thermodynamic propensity to form Z-DNA and the location of B/Z junctions, and that CG-repeats play an active role tuning this intrinsic B- DNA flexibility.
Incorporation of CC steps into Z-DNA: interplay between B-Z junction and Z-DNA helical formation.
A method for characterizing sequence-specific preferences for Z-DNA formation and B-Z junction localization within heterogeneous DNA duplexes is developed that is based on combining 2-aminopurine fluorescence measurements with a new quantitative application of circular dichroism spectroscopy for determining the fraction of B- versus Z- DNA.
Molecular biology: DNA twists and flips
The determination of the crystal structure of the junction between left-handed DNA and ‘normal’, right-handedDNA or B-DNA is determined, showing that the junction is very tight, and that a base pair is pushed out of the double helix, one base on each side of the Junction.
Z-DNA, an active element in the genome.
Accumulating experimental and clinical evidence support the idea that this non-B DNA conformation is involved in several important biological processes and may provide a target for the prevention and treatment of some human diseases.
Unveiling the pathway to Z-DNA in the protein-induced B–Z transition
This study shows the stable B* state supports the active picture for the protein-induced B–Z transition that occurs under a physiological setting and quantitatively determines quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences.
Protein-induced B-Z transition of DNA duplex containing a 2'-OMe guanosine.
Energetics of Z-DNA binding protein-mediated helicity reversals in DNA, RNA, and DNA-RNA duplexes.
The use of single-molecule fluorescence resonance energy transfer (FRET) is used to determine the energetics of Z-form stabilization by ZBP for DNA, RNA, and DNA-RNA duplexes, revealing that the formation of B-Z or A-Z junctions dominates the thermodynamics and kinetics of Z -form stabilization.


Structure of the DLM-1–Z-DNA complex reveals a conserved family of Z-DNA-binding proteins
It is found that the tumor-associated protein DLM-1 contains a domain with remarkable sequence similarities to ZαADAR, suggesting the existence of a family of winged-helix proteins sharing a common Z-DNA binding motif.
Crystal structure of the Zalpha domain of the human editing enzyme ADAR1 bound to left-handed Z-DNA.
The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Zalpha, which is specific for left-handed Z- DNA, and the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Zalpha to contact Z-DNA.
A-form conformational motifs in ligand-bound DNA structures.
The collective data provide new structural details on the conformational pathway connecting A and B-form DNA and illustrate how both proteins and drugs take advantage of the intrinsic conformational mechanics of the double helix.
The length of a junction between the B and Z conformations in DNA is three base pairs or less.
Raman experiments on the deoxyoligonucleotides d(CGCGCGC GCGCGCGAAAAA) and d(D(C GCGCGAAA) and their complements are found the latter compound cannot be induced into the Z form in saturated salt solution but that the former sequence goes into a B-Z junction at 5.5 M salt.
Z-DNA-binding proteins can act as potent effectors of gene expression in vivo
The role of Z-DNA-binding proteins in vivo is explored in yeast and it was found that even in the absence of the activation domain there is substantial transcription of the reporter gene if the Z- DNA-binding protein is expressed in the cell.
Structure of a B-DNA dodecamer: conformation and dynamics.
The crystal structure of the synthetic DNA dodecamer d(CpGpCpGpApApTpTpCpGpCpG) has been refined to a residual error of R = 17.8% at 1.9-A resolution (two-sigma data). The molecule forms slightly
Potassium permanganate as an in situ probe for B-Z and Z-Z junctions.
A chemical probe assay to detect and quantitate left-handed Z-DNA structures in recombinant plasmids in growing E. coli cells that can in principle be used for any unusual DNA structure that contains a restriction recognition site inside or near the structural alteration.