Chemistry Nobel Goes to Gene Transcription

By Robert F. Service
ScienceNOW Daily News
4 October 2006

A Californian whose father won the Nobel Prize 47 years ago earned this year's Nobel Prize in chemistry for uncovering the inner workings of the principal enzyme that converts DNA into RNA, a process known as transcription. Roger Kornberg, a structural biologist at Stanford University School of Medicine in Palo Alto, California, earned sole possession of the $1.37 million award for his decades of effort that culminated in 2001, when he reported the first molecular snapshot of an enzyme called RNA polymerase II (pol II) in action (Science, 20 April 2001, p. 411). This glimpse and others like it have revealed in exquisite detail the first step in biology's central dogma that genetic information in DNA is converted into RNA and then into proteins.

It's been a banner week for Stanford as well as Kornberg's own family. On Monday, Stanford geneticist Andrew Fire shared the physiology or medicine prize for his part in revealing that snippets of RNA can inactivate genes (ScienceNOW, 2 October). Kornberg's father Arthur shared the 1959 physiology or medicine prize for helping show how DNA is copied and passed down from mother to daughter cells. The younger Kornberg was 12 years old at the time. "I have felt for some time that he richly deserved it," says the senior Kornberg--an emeritus professor at Stanford--of his son's work. "His work has been awesome." The Kornbergs are the sixth set of parents and children to share the Nobel Prize. The junior Kornberg is slated to collect the Nobel at a December ceremony in Stockholm.

Biology's central dogma of "DNA-to-RNA-to-protein" has been around for decades, of course, but it's taken that long for some of the most critical details to be worked out. By the 1960s, researchers had found the process by which the enzyme RNA polymerase transcribes genetic information in bacteria and other simple organisms known as prokaryotes. But it took longer to appreciate that gene transcription is far more complex in eukaryotes, higher organisms that include all plants and animals. In the late 1980s, Kornberg's lab purified an eukaryotic transcription complex from yeast that included pol II and five associated proteins called general transcription factors. To their surprise, this complex didn't respond to other proteins known to activate specific genes. That discovery led them to another key molecular player known as "mediator"--a complex of some 20 proteins that helps bridge the work of pol II with proteins that turn on specific genes.

Kornberg's lab then went on to visualize just how those proteins work by producing a series of x-ray crystal structures of pol II bound to DNA, RNA, and other proteins that make up the machinery of transcription. "Kornberg has given us an extraordinarily detailed view of this machine, which is essential for life," says Peter Fraser, who heads the laboratory of chromatin and gene expression at the Babraham Institute in Cambridge, U.K.

In a press conference, Kornberg said he had known in recent years that it was "not out of the realm of possibility" that he would win a Nobel. However, it still came as a shock. "It's not something you ever expect," he says.