Wednesday, March 21, 2007

Nobel Laureate: Roger Kornberg


The Nobel Prize in Chemistry 2006.

"for his studies of the molecular basis of eukaryotic transcription"

Roger Kornberg won the Nobel Prize in 2006 for describing for the first time the structure of eukaryotic RNA polymerase II at the atomic level. The presentation speech summarizes this achievement.
This year's Laureate in Chemistry, Roger Kornberg, has studied what the transcription apparatus looks like in eukaryotes, organisms with cells that have a defined nucleus, which include all fungi, plants and mammals, human beings as well. In choosing the model system for his studies he swam against the stream and selected baker's yeast, which is one of the simplest eukaryotes. This was a crucial choice, as yeast cells offer a number of advantages in this endeavour compared to the cells from mammals that had previously been used. For instance, it is possible to cultivate yeast on a large scale and to benefit from the simplicity with which yeast cells can be modified genetically. The transcription apparatus in yeast cells is very similar to the corresponding system in mammal cells, which suggests that it came into being at a very early stage of development.

By combining biochemical methods and a depiction technique called X-ray crystallography, Roger Kornberg succeeded in producing particularly detailed molecular models of the transcription apparatus in yeast cells. These models are so detailed that individual atoms can be discerned. Through the study of a host of different models of the transcription apparatus both on its own and while fully engaged in copying DNA to RNA, Kornberg has been able to draw new, important conclusions about the mechanisms of transcription and how it is regulated. As a result of his study we now understand, for instance, how the transcription apparatus chooses where to start copying on the DNA strand, how it selects the correct RNA building blocks and how it moves along the DNA strand while the copy is being made.
This was such an important result that it easily made the cover of Science magazine when the structure was published in June, 2001. There were two back-to-back papers from the Kornberg lab in that issue. (The papers were available online in late April.) As the presentation speech says, they choose to work with the enzyme from yeast because it is easy to manipulate genes in yeast cells. The first paper presented the structure of yeast RNA polymerase II in the form it would take during intitiation. The second paper described the elongation form of the enzyme [see Transcription].

RNA polymerase II [see Eukaryotic RNA Polymerases] is a complex molecule with 12 different subunits. Two of them are dispensible and they were not present in the crystals that Kornberg solved. The core of the enzyme is formed from the large subunits Rpb1 and Rpb2. These are the homologues of the β and β′ subunits of the bacterial enzyme and homologous subunits are found in RNA polymease I and RNA polymerase III. The other subunits (e.g., Rbo5, Rpb9) are much smaller. They make numerous close contacts with the large core subunits to form a very compact structure.

The technical achievement represented by these structures cannot be underestimated. While there are other examples of large complexes whose structures have been solved by X-ray crystallography, this was a particularly difficult case and it took about ten years to get the result that was published in the June 2001 issue of Science.

Roger is the son of Arthur Kornberg who won the Nobel Prize in 1959 for the discovery of DNA polymerase. This is the seventh parent-offspring set of Nobel Prizes—a remarkable statistic, if you think about it. Roger's brother is Tom Kornberg who studies Drosophila development at the University of California, San Francisco. They have another brother Ken—the smart one!—who's an architect.

The Stanford University site has a photo of Roger with his father and a short video clip of Roger Kornberg at the Press Conference.

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