Structural Biochemistry/Nucleic Acid/DNA/Watson and Crick

Race to Discovery
After the Hershey-Chase experiment confirming that DNA was in fact the genetic material, the chase for the structure of DNA was on. In 1953, Watson and Crick published their article "Molecular structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid", which made them the first scientists to publish the structure of DNA as a double helix. Watson and Crick felt that Linus Pauling, who had published the alpha helix structure of proteins and later published an incorrect version of DNA’s structure, was their main competitor in determining the structure of DNA. At the time Pauling was one of the few men in the scientific community who pondered the importance of DNA structure. Watson, with a genetic background, believed similarly. Watson found a new way to investigate the structure of DNA by means of x-ray diffraction when he visited Maurice Wilkin's lab. However, since he did not possess enough knowledge about x-ray crystallography, he took the time to learn about the procedures at Cavendish in 1951. He shared an office at the time with a man who was a crystallography expert, Mr. Francis Crick. Soon, Watson intrigued Crick to the point that the two joined forces in the race for the double helix.

Importance of Discovery
Their discovery shed light on how genetic material could be passed on from generation to generation, and proved the simplicity of the transfer of genetic material. Our present understanding of the storage and utilization of a cell’s genetic information is based on work made possible by this discovery.

DNA Structure – leading to function
Within Watson and Crick's article they claim that DNA is a double helical structure and that Pauling's previous attempt to define the structure noting that it did not have the much needed hydrogen bond stabilization and underestimated the van der waals interactions of base stacking. The helix would of right handed as the two chains run in opposite directions. Bases were linked towards the inside of the helix and the sugar phosphate linkage created the outer backbone. The helix would repeat every 10 residues or 3.4 Angstroms, as they saw in the crystallographic data from Rosalind Franklin. The diameter of the helix was found to be 20 Angstroms and there was a rotation of 36 degrees per base, thus having 10 bases every 360 degrees. The most innovative ideas of Watson and Crick's model was that the two chains were held together by bases of purines and pyrimidines. By hydrogen bonding, a purine must be bonded to a pyrimidine creating a complementary pair. Using experimental data that showed the ratios of adenine and thymine were very close as were guanine and cytosine they stated that adenine bonds to thymine and guanine binds to cytosine. They discovered this based on comparing the ratios of A-T, C-G and A-G, and they found that the first two ratios were the closest to 1 where as the second was varied. This helped them make the conclusion that A bonds with T and C bonds with G only. The pairs’ base lengths are equal, and fit exactly between the two chains of phosphates. The bonds between the two phosphate groups are hypothesized by Watson and Crick to be hydrogen bonds, which are easily broken. The DNA nucleotide must also contain deoxyribose and not ribose because the extra oxygen on ribose would interfere with the structure due to van der waals interactions. The discovery of DNA structure thus gave them a very good idea on how DNA might replicate itself, and thus the passing of genetic material. Also, they found that each of the bases was capable of tautomerizing between the enol and keto forms. Experimentally, it was determined that the keto form predominates at a physiological pH. Thus, they also came up with a method for demonstrating how DNA may denature as pH changes due to conversion from the keto to the enol form.

Later discoveries
Watson and Crick’s discovery led to many new investigations, such as how DNA contains all the information for protein production, as well as the human genome project, whereby all human genes are attempted to be mapped.