If Watson and Crick unlocked the mystery of DNA's structure, then Stanford University's Roger Kornberg and his team unzipped the secret of how the cell converts DNA into the RNA needed to make proteins. The award of this year's Nobel Prize for Chemistry to Kornberg emphasis just how important his discoveries are in cancer, heart disease, genetic disorders, and stem cell research.

DNA secretes the genetic code for all organisms with a nucleus in their cells, so-called eukaryotes, from microbial yeast to mammalian yak by way of a multitude in between, including human beings. It was known from the 1950s that ribonucleic acid, RNA, acts as DNA's messenger, traversing the nuclear border in the cell to reveal the code to the protein-making machinery. The enzyme responsible for transcribing the unzipped DNA double helix into RNA, RNA polymerase, was itself revealed in 1959. However, eukaryotes, unlike bacteria, which have no cell nucleus, utilize three different forms of the enzyme. This eukaryotic complexity confused the issue throughout the following decades with clues emerging slowly over this period.

Kornberg followed these various clues from his time as a post-doctoral researcher with the Cambridge MRC under Francis Crick and Aaron Klug, until he returned to Stanford U. At that point, he was focusing on the transcription process in one of the simplest eukaryotes, baker's yeast, Saccharomyces cerevisiae. Using baker's yeast as a model of all eukaryotic organisms, Kornberg duplicated the yeast transcription system in the proverbial test-tube by combining highly purified RNA-polymerase II and the necessary five general transcription factors TFIIB, E, F, H, and the TATA-binding protein (TBP).

It was not until researchers identified the missing component that would allow it to be activated that the real insights began to emerge. In order to function, the transcription system requires a complicated structure composed of about twenty different proteins working together. Having isolated this multiprotein complex, known as Mediator, the research moved forward rapidly as the inner workings of the yeast transcription system emerged.

The next obstacle was to obtain atom-by-atom molecular structures showing the process of transcription in action. For this, Kornberg and his colleagues were forced to develop novel crystallization techniques that could handle the half a megadalton RNA polymerase on which the whole system hinges. With suitable crystals to hand, the powerful X-ray source at the Stanford Synchrotron Radiation Facility provided the high-resolution X-ray images of the transcription components, and a detailed solution to more than twenty year's work. The results were published in two seminal papers in the journal Science. At the time, Kornberg's former mentor, Aaron Klug, described the work as "A far-reaching stride toward comprehending the enzymatic mechanism underlying transcription. So great is its power when combined with biochemistry and genetics that we should eventually even be able to see Mediator regulating the enzyme complex. We look forward to further chapters in the saga of this voyage of discovery."

Nevertheless, Kornberg was surprised to hear from Sweden on October 4 and was astounded to learn from his daughter that he already had 156 missed calls on his cell phone by six in the morning. "Part of the pleasure and the fascination of what we do has been in discovering the mechanics, the inner workings of that machine," he said on learning he was to receive the Prize.

http://kornberg.stanford.edu/

http://nobelprize.org/nobel_prizes/chemistry/laureates/2006/

http://nobelprize.org/nobel_prizes/medicine/laureates/1959/