DNA Cliffhanger

It's not up for an Oscar, but a flick from a performer new to the silver screen is winning rave reviews. The 8-second clip, aired in Kansas City, Missouri, today at the annual meeting of the American Physical Society, shows the first sequential images of an enzyme sliding down a strand of DNA. The film is a tantalizing first glimpse of how researchers might someday study enzymes in action or watch how mutations cause genes to go awry.

While electron microscopes can make high-resolution images of DNA and RNA, those techniques have big drawbacks: The samples must be stained and motionless. Such images are "like snapshots of a ballerina," says Paul Hansma, a physicist at the University of California, Santa Barbara. "They won't tell you about the ballet."

Hansma and colleagues at Santa Barbara and the University of Oregon were intent on crashing the ballet. Using an atomic force microscope (AFM), an instrument with a touch gentle enough not to disturb a busy molecule, Hansma's group took pictures of an enzyme, RNA polymerase, ratcheting one DNA strand through itself. The enzyme links nucleotide bases to create RNAs that serve as templates for proteins.

The AFM's fine tip detects the attraction between atoms as it taps its way across the surface of a sample. The technical challenge is to anchor the molecules without hampering their activity. After several attempts, the team found that zinc ions added to the water would attach the molecule to the sample dish. That allowed the DNA strand to wiggle but not so much as to blur the image. But the team also had to slow down the enzyme, because the AFM needs at least 40 seconds to take a picture 200 nanometers across. By putting fewer nucleotide bases into solution, the researchers reduced the polymerase's transcribing speed from about 45 bases per second to 1 base per second. That gave them about 10 minutes as the enzyme worked its way down a 600-base-pair DNA strand.

Experts are impressed with the video. At a preview in Texas last year, biologists in the audience "were all on the edges of their seats," says Mike MacLeod, a molecular biologist at the M. D. Anderson Cancer Center in Houston. Although the AFM remains an exotic tool to most biologists, the payoff of using it could be huge: Researchers might be able to interpret subtle changes in the shape of RNA polymerase as it passes over each letter of the genetic code to read off the order of bases in a genome. And that, says Hansma, "would revolutionize the sequencing of DNA."