At the level of detail the group obtained, some intriguing structures came to light, offering the first real understanding of the defining events of transcription. They saw a docking site that might reveal the starting point of transcription, a spot where the RNA polymerase is correctly situated on a gene. They also saw something completely unexpected: a "finger" of the helper factor protein that pokes into the enzyme's active center. The researchers speculate that the poking action may help slow down the transcription process so that the strands of DNA and newly made RNA can separate properly.
"This turned out to be quite interesting. No one had even speculated about it before," said David Bushnell, PhD, a research associate and first author of one of the papers. "We think the protrusion reaching into the enzyme makes sense of a lot of genetic and biochemical data that people were scratching their heads over. Figuring out the structure gave remarkable context to years of hard work by many people."
The second paper describes how the team caught a snapshot of the polymerase in action, something that hadn't been done before. Kenneth Westover, an MD/PhD student and first author of the second paper, developed a method in which the newly made RNA could be visualized coming off the DNA.
"When we look to see where the two separate, we find that lo and behold, the RNA passes through a hole and the DNA comes out over the top," said Kornberg. "The separation that is achieved at the hole is revealed for the first time in this paper."
How the strands of RNA and DNA are pushed apart has a simple physical explanation: the RNA polymerase inserts itself as a wedge between the two, with the RNA trailing out the hole. That same opening is the one that the protein finger dips into. "One might have imagined this, but to see it is a
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Contact: Mitzi Baker
mitzibaker@stanford.edu
650-725-2106
Stanford University Medical Center
12-Feb-2004