Sunday, March 30, 2008

structure of DNA

Using X-rays to See Through DNA

"Photograph 51". X-ray diffraction photo of a DNA molecule, structure B,
Photo: Cold Spring Harbor Laboratory Archives

Watson and Crick used stick-and-ball models to test their ideas on the possible structure of DNA. Other scientists used experimental methods instead. Among them were Rosalind Franklin and Maurice Wilkins, who were using X-ray diffraction to understand the physical structure of the DNA molecule.

When you shine X-rays on any kind of crystal – and some biological molecules, such as DNA, can form crystals if treated in certain ways – the invisible rays bounce off the sample. The rays then create complex patterns on photographic film. By looking at the patterns, it is possible to figure out important clues about the structures that make up the crystal.


A Three-Helical Structure?

Model of the alpha helix, 1951. Photo: Oregon State University's Special Collections

The scientist Linus Pauling was eager to solve the mystery of the shape of DNA. In 1954 he became a Nobel Laureate in Chemistry for his ground-breaking work on chemical bonds and the structure of molecules and crystals. In early 1953 he had published a paper where he proposed a triple-helical structure for DNA. Watson and Crick had also previously worked out a three-helical model, in 1951. But their theory was wrong.

Their mistake was partly based on Watson having misremembered a talk by Rosalind Franklin where she reported that she had established the water content of DNA by using X-ray crystallographic methods. But Watson did not take notes, and remembered the numbers incorrectly.

Instead, it was Franklin's famous "photograph 51" that finally revealed the helical structure of DNA to Watson and Crick in 1953. This picture of DNA that had been crystallized under moist conditions shows a fuzzy X in the middle of the molecule, a pattern indicating a helical structure.


Specific Base-Pairing

The base-pairing mystery had been partly solved by the biochemist Erwin Chargoff some years earlier. In 1949 he showed that even though different organisms have different amounts of DNA, the amount of adenine always equals the amount of thymine. The same goes for the pair guanine and cytosine. For example, human DNA contains about 30 percent each of adenine and thymine, and 20 percent each of guanine and cytosine.

With this information at hand Watson was able to figure out the pairing rules. On the 21st of February 1953 he had the key insight, when he saw that the adenine-thymine bond was exactly as long as the cytosine-guanine bond. If the bases were paired in this way, each rung of the twisted ladder in the helix would be of equal length, and the sugar-phosphate backbone would be smooth.

Structure Shows Action

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material" wrote Watson and Crick in the scientific paper that was published in Nature, April 25, 1953.

This was indeed a breakthrough in the study of how genetic material passes from generation to generation. Once the model was established, its mere structure hinted that DNA was indeed the carrier of the genetic code and thus the key molecule of heredity, developmental biology and evolution.

The specific base pairing underlies the perfect copying of the molecule, which is essential for heredity. During cell division, the DNA molecule is able to "unzip" into two pieces. One new molecule is formed from each half-ladder, and due to the specific pairing this gives rise to two identical daughter copies from each parent molecule.


http://nobelprize.org/educational_games/medicine/dna_double_helix/readmore.html

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