Z- DNA: An Undergraduate’s Perspective
Tyson D. Bowen
Abstract
In 1979, Alexander Rich discovered Z-DNA. It is a left-handed DNA helix with several distinct features, notably a single groove; guanine in the syn position; purine-pyrimidine alternation; and a tighter zig-zagging phosphate backbone. Z-DNA is stabilized by a number of different mechanisms and molecules. Existing in a solution of B-DNA, Z-DNA formation prompts two B-Z interactions for every segment of Z-DNA. These interactions each have two extruded bases that may serve as recognition sites. The function of Z-DNA is still an area of intense research, but current studies indicate a role in gene regulation and transcription. Additionally, Z-DNA might increase mutagenesis and cancer. A family of proteins has also been discovered that recognizes Z-DNA because of its unique conformation, not its sequence. Using these proteins Z-DNA has been incorporated into synthetic DNA as a chimeric restriction endonuclease. Future research on Z-DNA might be used to better understand the human genome, treat small pox, and cure cancer.
Background
The structure of DNA, they very molecule of life, was not known until 1953, when it was elucidated by James Watson and Francis Crick (Watson and Crick 1953a; Watson and Crick 1953b). They proposed a right-handed double helical molecule that was thought to be the only conformation of DNA until 1979 when Alexander Rich and his team inadvertently discovered ZZ- DNA: An Undergraduate’s Perspective DNA (Wang and others 1979). They were attempting to study crystallized DNA fragments due to the limitations imposed by the traditional X-ray diffraction techniques. The crystallized fragments used a fixed sequence, d(CpGpCpGpCpG) in this experiment, to solve the 3D structure at atomic resolution. To the team’s surprise the deoxy hexamer formed two distinct conformations depending upon the salt concentration. At low salt concentration, the expected B-DNA of Watson and Crick formed. But at high salt concentrations a radical conformation formed. The DNA adopted a lefthanded double helix form with a zig-zag patterned phosphate backbone, leading to the name Z-DNA (Gagna and Lambert 2003; Mark 1985; Wang and others 1979). Before this discovery, all biological helixes were thought to be righthanded (Zhang 2003). However, Z-DNA was initially thought to be “molecular junk” or a mere chemical oddity, but Rich and his colleagues kept up the research and were able to determine that Z-DNA plays several key roles (Gagna and Lambert 2003; Rich and Zhang 2003). This discovery launched a torrent of new research into the now dynamic form of DNA. This conformational discovery helped to prove that DNA is an extremely dynamic molecule existing as an equilibrium of conformations (Gagna and Lambert 2003).
Introduction
The traditional form of DNA discovered by Watson and Crick is now known as B-DNA. DNA is now known to be a highly active molecule, adopting a variety of other forms, most of which are right-handed helixes (Gagna and Lambert 2003; Zhang 2003). The right-handed, but dehydrated A-DNA and the right-handed C-DNA that exists in solvents are two of the more common known deviations (Gagna and Lambert 2003). Z-DNA is in a class of its own, however. Apart from its left-handed structure, it has many other distinctive features that set it apart from the common B-DNA (Wang and others 1979). But Z-DNA exists alongside B-DNA and the other conformations in the cell, providing a number of B to Z transition sites in any given genome (Arndt-Jovin and others 1983)....continued in print edition.
