Watson and Crick may have come up with their structure for DNA with help from Franklin's crystallographic data more than fifty years ago but it was not until the 1980s that this structure was shown beyond reasonable doubt to be a double helix. However, revealing its double helical says nothing about the structure of all possible base sequences. Now, US researchers have made a significant advance in our understanding of life's main molecule.

	Pui Shing Ho

Structure is all when it comes to molecules, but it is next to impossible to predict the structure of biomolecules despite their having only a limited number of building blocks. Whole research programs are run simply to predict the structure of proteins, such as enzymes and receptors from a known sequence of amino acids. The nucleic acids, DNA and RNA are no less a problem even though their chemical alphabet is limited to just four units in each, compared with the 20 amino acids usually found in proteins.

Now, biochemist-biophysicist Pui Shing Ho and colleagues at Oregon State University are well on their way towards using X-ray crystallography to determine the three-dimensional structures of nearly all the possible sequences of a macromolecule. The Oregon team has investigated all permutations of a specific piece of repeating DNA labeled "d(CCnnnN6N7N8GG)". In this sequence N6, N7, and N8 are any of the four naturally occurring nucleotides. Ho explains that currently 63 of the 64 possible permutations of these sequences have been crystallized from a defined set of solutions.

This, the researchers claim, has allowed them to plot a map of the structure of DNA sequences based on the nucleotide sequence itself. "We are only half way there," Ho told Reactive Reports, "This paper is a proof of concept that such an under taking is feasible and can provide a significant amount of information." Nevertheless, Ho's work could have implications for understanding the biological function of genes and in particular the processes of gene expression, mutation and repair, and why some DNA structures are inherently prone to damage.

	Click image to magnify

"There can be 400 million nucleotides in a human chromosome, but only about 10 percent of them actually code for genes," Ho explains, "The other 90 percent of the nucleotides may play different roles, such as regulating gene expression, and they often do that through variations in DNA structure."

"Now, for the first time, we're really starting to see what the genome looks like in three-dimensional reality, not just what the sequence of genes is," Ho said. "DNA is much more than just a string of letters, it's an actual structure that we have to explore if we ever hope to understand biological function. This is a significant step forward, a milestone in DNA structural biology."

Proc Natl Acad Sci, 2005, in press; http://dx.doi.org/10.1073/pnas.0409455102

http://www.pnas.org/cgi/content/full/98/13/7265 - earlier related work

http://www.pnas.org/cgi/content/full/121176898/DC1/1 - movie

http://oregonstate.edu/dept/biochem/faculty/ho.html

http://en.wikipedia.org/wiki/Dna