DNA's Twist

Structure Biology

Scientists have known for more than a quarter-century that DNA, which is typically right-handed, can twist itself into an alternative, left-handed conformation. Now, an X-ray crystallographic study of the junction between these right- and left-handed forms opens the door to better understanding of how genomic DNA performs such contortions—and to what purpose.

The 2.6- structure was solved by MIT biologist Alexander Rich; Yang-Gyun Kim of Chung-Ang University and Kyeong Kyu Kim of Sungkyungkwan University, both in South Korea; and coworkers. It reveals that at the junction between right-handed, or B-form, DNA and left-handed, or Z-form, DNA, just a single base pair is broken and flipped out of the double helix. From this observation, the researchers conclude that the junction conserves both energy and helical structure (Nature 2005, 437, 1183). The work suggests that transient regions of left-handed DNA frequently form in our chromosomes, Rich argues.

Natures design of the B-Z junction maximizes helix integrity and base pairing, thereby minimizing the impact of the dramatic alteration in helix structure when Z-DNA forms in a chromosome, notes biologist Richard R. Sinden of the Texas A&M University System Health Science Center in an accompanying commentary. The teams success in using a Z-DNA-binding protein to stabilize Z-DNA long enough for crystallographic analysis may help us to elucidate what Z-DNA is doing within the B-DNA that makes up chromosomes, he adds.

Rich first observed the structure of Z-DNA and its unusual zigzagging more than a quarter-century ago. Evidence of its biological function was slow to emerge, and although Z-DNA continued to intrigue chemists, biologists largely regarded Z-DNA as a novelty. Still, Rich and a few others persisted in studying Z-DNA and accumulated evidence that the torsional strain generated by transcription or the unwrapping of genomic DNA from its packaging generates transient regions of Z-DNA. More recent studies have suggested that these transient tracts play a key role in both virus pathogenesis and gene expression.

Computational chemist Thomas E. Cheatham III of the University of Utah notes that although the new structure does not show the biological function of the B-Z junction per se, it will allow scientists to model how Z-DNA might result from torsional strain. Rich tells C&EN his lab has already started thinking about this problem. He also hopes to determine whether the pair of extruded bases at the junction might be particularly susceptible to oxidative damage or might provide a signal for recruitment of proteins.

Nadrian C. Seeman, a chemist at New York University who has constructed nanomechanical devices driven by the transition between B-DNA and Z-DNA, notes that the structures impact will extend beyond biology. The atomic coordinates of this junction will now enable DNA nanotechnologists to model properly those sites where B-DNA and Z-DNA abut each other in nanomechanical devices, he says.