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

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Abstract
The existence of left-handed DNA (or Z-DNA) was reported in 1979, and marked by a Nature cover. This week's cover story is the determination of the crystal structure of the junction between left-handed DNA and ‘normal’, right-handed DNA or B-DNA. Each time a DNA segment turns to Z-DNA, two of these B–Z junctions are created. Z-DNA often forms transiently during transcription and other physiological processes, then relaxes to the less energetic B form. The three-dimensional structure shows 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. This adjustment maintains the base stacking that is a major stabilizing factor. These displaced bases may be sites for DNA modification. On the cover, a molecule containing a B–Z junction is shown in the centre, with Z-DNA, naturally, to the left and B-DNA to the right. 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.