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Chemist’s Nobel prize for gene-reading breakthrough

Roger Kornberg spent 20 years patiently unravelling the process by which genes are "read", a central cog in the machinery of life

A chemist who has spent 20 years unravelling the process by which genes are 鈥渞ead鈥 was today awarded the Nobel prize for chemistry.

Through his detailed studies of the underlying chemistry, Roger Kornberg of Stanford University in California, US, deepened understanding of the first, vital step of gene reading, called transcription.

鈥淚鈥檓 simply stunned, there鈥檚 no other words,鈥 said Kornberg after receiving the call at 0230 this morning.

Kornberg鈥檚 father, Arthur, won the Nobel prize for medicine in 1959 for his work showing how DNA is copied when cells multiply.

Transcription is the mechanism by which the DNA of a gene is copied into a single strand of genetic material called messenger RNA (mRNA). It is one of the steps in the process by which the cells make proteins from DNA.

鈥淚f the secret of life could be likened to a machine, the process of transcription would be a central cog in the machinery that drives all others,鈥 says Peter Fraser of the Babraham Institute in Cambridge and senior fellow of the UK Medical Research Council. 鈥淜ornberg has given us an extraordinarily detailed view of this machine, which is essential for all life.鈥

Genetic recipe

In the process itself, the mRNA鈥檚 鈥減hotocopy鈥 of the original gene is transported out of the cell nucleus into another part of the cell called the ribosome. Here, the mRNA serves as the recipe for making the protein for which the original gene codes.

When the process goes wrong, it can result in a multitude of diseases and abnormalities, from cancer and birth defects to diabetes and inflammation. So, by understanding the process at a more detailed level, researchers hope to develop new treatments for disease.

Kornberg has done much to show how the process is more complicated in advanced 鈥渆ukaryotic鈥 organisms with a well-defined nucleus, than it is in simpler life forms, such as bacteria.

His key contribution, in 2001, was to demonstrate the chemical structure of RNA polymerase II, the key enzyme at the heart of transcription.

Through detailed investigations of the structure of yeast RNA polymerase II, Kornberg showed how the gene to be transcribed is fed like ticker tape into the enzyme, emerging the other side with a growing strand of mRNA attached.

Since then, he and his colleagues have unravelled structures of other components of the process, such as the method by which strands of DNA and mRNA are unzipped to free the mRNA strand.

Mediated process

They have also probed the molecular details of other components vital for the process, such as the transcription 鈥渇actors鈥 which serve as switches to activate a particular gene.

Further studies in 2004 showed how the nucleotide base units from which mRNA is built are fed into the enzyme one by one to assemble the mRNA strand.

More recently, Kornberg鈥檚 lab has been unpicking the process by which a component in the process, called 鈥淢ediator鈥, serves as an exchange, telling RNA polymerase II which genes to transcribe.

Cash prize

鈥淭hese are much the largest structures ever to have been resolved at this level of detail,鈥 says Julian Downward, associate director of Cancer Research UK鈥檚 London Research Institute. 鈥淭he award of the Nobel prize is a very fitting reward for this immensely important work.鈥

The ultimate prize is to establish in fine detail how each and every gene is controlled and regulated, and how the process can be corrected through new medical treatments when it goes awry and causes disease.

Kornberg is the sole recipient of the chemistry prize, which is worth 10 million Swedish krona ($1.37 million).