This high-speed copying makes all life possible. The enzymes in charge do an incredible job, getting the sequence in humans correct more than 99.999 percent of the time. But new evidence from the laboratory of Eric Kool at the University of Rochester shows that the formation of hydrogen bonds is not as important as scientists expected. Their latest evidence appears in the June 17 issue of Nature. The bases must fit together for a polymerase enzyme to copy them.
Shape brings fidelity to the process.
In the paper, Kool and former postdoctoral associate Tracy J. Matray, now at Geron Corp., designed two radically different shapes for a base pair. 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 a little bit like an odd couple that blends into a conventional neighborhood by canceling out each other's foibles. 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. One possible application of the current work, Kool says, is a test for cancer-causing agents that cause mutations by knocking out a single base, which is the most common form of mutation in our bodies.