Chemistry professor makes DNA discovery

Kool

N ew evidence from the laboratory of Eric Kool, professor of chemistry at the College, shows that the formation of hydrogen bonds between the two rows of bases of DNA is not as important in the DNA process as scientists expected. Instead, shape is paramount. Together, a pair of bases must fit into its assigned space in the larger DNA molecule so that it can serve as a template for identical molecules. Kool's evidence appeared in the June 17 issue of Nature.

"This is the jigsaw-puzzle model of DNA," said Kool. "The bases must fit together for a polymerase enzyme to copy them. Shape brings fidelity to the process." The finding is a surprise to many biochemists who have long focused on hydrogen bonds when trying to unravel the operation of polymerase enzymes, which copy DNA.

The Nature paper is the latest in a series of publications and patents in which Kool describes experiments with molecular mimics: synthetic molecules his laboratory creates to substitute for the conventional bases (adenine, cytosine, thymine, guanine) that form the DNA of all known life forms. This latest paper describes an experiment in which Kool and former postdoctoral associate Tracy Matray designed two radically different shapes for a base pair. With funding from the National Institutes of Health and the U.S. Army, they reduced one base to the smallest chemical entity--a proton--and provided it with a partner that was nearly double the size of a normal base. Together, the two bases filled about the same space as a conventional pair, fitting within the general structure of DNA, though neither looks anything like a traditional base.

"It's amazing that although these bases look totally foreign, as long as they fit together properly, like two jigsaw puzzle pieces, enzymes perceive them as part of a DNA molecule and copy them accordingly. Not only do you not need hydrogen bonds to copy DNA, you don't even need the traditional shape of the individual bases," said Kool.