Fri, Oct 06, 2006 page7

• New chemistry laureate saw how to read code of life

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  If DNA is the blueprint for life, RNA is the builder that has to make something out of it, and Nobel chemistry winner Roger Kornberg figured out how this happens.

  Kornberg made an image of a molecule that RNA uses to read and transcribe the DNA code into something that actually works.

  It took close to 20 years to find a way to first see and then understand the molecule, known as RNA polymerase. Kornberg used a method called X-ray crystallography to freeze the atoms, and image them as they moved, step by step.

  

  Roger Kornberg, left, of Stanford University, smiles with his father, Arthur, right, on the Stanford, California, campus, on Wednesday. Roger won the Nobel Prize in chemistry on Wednesday, while his father won the Nobel Prize in medicine in 1959.

  PHOTO: AP

  DNA is clearly important, Kornberg says.

  "But on its own, this information is silent," he has said. "RNA polymerase gives it voice."

  This copying process is called transcription, and it requires a complicated physical structure that, like machines on a construction site, shifts pieces around -- all at the atomic level.

  "This is a machine with moving parts," Kornberg said in a statement released by Stanford University, where he works, in 2000. His team uses terms such as "jaws," "clamp" and "funnel" to describe the pieces.

  The structure forms pincer-like jaws that trap the DNA near the gene to be transcribed. A clamp then swings over the DNA and locks on.

  "This is one of the most fundamental biological processes," said Jeremy Berg, director of the National Institute of General Medical Sciences, one of the US National Institutes of Health, which helped fund Kornberg's work.

  "The DNA double helix is a very beautiful structure but it is a challenge to deal with because all the information is inside," Berg said in a telephone interview.

  "What RNA polymerase has to do is somehow find the right spot and then pull the two strands of the double helix apart in the right region," he said. "Then it uses RNA polymerase to make polymerase."

  Polymerase is an enzyme that can cut apart these structures.

  "It has to copy the sequence very accurately. It has to stop and start in the right places. It has to turn on the right genes under the right circumstances," Berg said.

  All cells carry a full set of DNA code, but each cell must activate, or express, different genes in order to do their specialized work.

  "So muscle cells express different genes than brain cells do and the assembly that does this is RNA polymerase," Berg said.

  Kornberg's team set out to visualize this structure.

  "When Roger Kornberg started working on it, it was so complicated, some people thought he was somewhere between ambitious and crazy to try to solve its structure," Berg said.

  "He very steadily and methodically did the chemistry and tried to figure out what the components were and tried to handle this delicate assembly or set of assemblies."

  Kornberg credited perseverance for the achievement.

  "While winning a Nobel Prize is always an honor, this one is extra special, because we worked so long," Kornberg said after a press conference at Stanford. "It required a real leap of faith to sustain. The work took 20 years."

  Kornberg's father, Arthur, whose work in genetics won him a Nobel Prize in 1959, added an aptly succinct perspective, saying: "Everything is in the genes."

  Kornberg was 12 years old when he went to Stockholm with his dad, who received the 1959 Nobel Prize in medicine.

  "I'll probably remember more of my father's ceremony than I will of mine, given everything that is going on around me," Kornberg said.
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