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


Left-handed Z-DNA is a higher-energy form of the double helix, stabilized by negative supercoiling generated by transcription or unwrapping nucleosomes1. Regions near the transcription start site frequently contain sequence motifs favourable for forming Z-DNA2, and formation of Z-DNA near the promoter region stimulates transcription3,4. Z-DNA is also stabilized by specific protein binding; several proteins have been identified with low nanomolar binding constants5,6,7,8,9. Z-DNA occurs in a dynamic state, forming as a result of physiological processes then relaxing to the right-handed B-DNA1. Each time a DNA segment turns into Z-DNA, two B–Z junctions form. These have been examined extensively10,11,12, but their structure was unknown. Here we describe the structure of a B–Z junction as revealed by X-ray crystallography at 2.6 Å resolution. A 15-base-pair segment of DNA is stabilized at one end in the Z conformation by Z-DNA binding proteins, while the other end remains B-DNA. Continuous stacking of bases between B-DNA and Z-DNA segments is found, with the breaking of one base pair at the junction and extrusion of the bases on each side (Fig. 1). These extruded bases may be sites for DNA modification.

Two bases have been extruded from base stacking at the junction. The white line goes from phosphate to phosphate along the chain. O is shown red, N blue, P yellow and C grey.

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Figure 2: Organization of the complex and electron density maps.
Figure 3: Skeletal stereo views of DNA.
Figure 4: Stereo skeletal view perpendicular to the bases covering the five central bases. C - 2, C - 1, A0, T1 and A2 are in one strand, T - 2′, A - 1′, T0′, G1′ and G2′ in the other.


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We thank T. Schwartz for discussions and technical advice. Use of the Pohang Light Source (PLS) was supported by MOST and POSCO. Use of the Spring-8 is supported by the Japan Synchrotron Radiation Research Institute (JASRI). K.K.K was supported by a Basic Science Research Grant from the Korea Research Foundation. A.R. acknowledges support from the National Institutes of Health and the Dana and Ellison Medical Foundations.

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Correspondence to Yang-Gyun Kim or Kyeong Kyu Kim.

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Coordinates and structure factor files have been deposited in the Protein Data Bank under accession number 2ACJ. Reprints and permissions information is available at The authors declare no competing financial interests.

Supplementary information

Supplementary Discussion

Additional discussion on the results of the study that could not be included in the main text. (PDF 88 kb)

Supplementary Methods

Additional details on the methods used in the study that could not be included in the main text. (PDF 108 kb)

Supplementary Tables

Supplementary Table 1: Data collection phasing and refinement statistics. Supplementary Table 2: Local base pair step parameters of B-Z DNA and standard B- and Z-DNA. Supplementary Table 3 RMS deviation (Å) among Zα domains. (PDF 162 kb)

Supplementary Figure S1

Overall structure of the B-Z junction containing DNA bound to hZαADAR1. (PDF 156 kb)

Supplementary Figure S2

Structural overlap of the Zα proteins bound to Z-DNA. (PDF 193 kb)

Supplementary Figure S3

Titration by CD spectrometry of the 17mer duplex with hZαADAR1. (PDF 124 kb)

Supplementary Figure S4

Stereo 2Fo-Fc omit maps of extruded nucleotides. (PDF 282 kb)

Supplementary Figure S5

A diagram illustrating the B-Z transition and the ensuing conformational changes. (PDF 693 kb)

Supplementary Figure S6

Structures of DNA including extruded bases. (PDF 83 kb)

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Ha, S., Lowenhaupt, K., Rich, A. et al. Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature 437, 1183–1186 (2005).

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