Thousands of times each second along the seven feet of DNA in every cell in our bodies, enzymes are busy moving along the molecule, ferrying the proper chemical bases into the appropriate positions to make copies of the genetic blueprint. 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.
How so? Scientists have long assumed that the demand for this high fidelity comes from the chemical bonds called "hydrogen bonds"between the two rows of bases of DNA. One nucleotide extends a chemical "handshake," and only its appropriate partner can match up with it, forming a pair of bases that take their place as one rung in the twisting ladder of the double helix.
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. 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. Their latest evidence appears in the June 17 issue of Nature.
"This is the jigsaw-puzzle model of DNA," says Kool, professor of chemistry. "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. In the
paper, Kool and former post-doctoral associate Tracy J. Matray, now at Geron
Corp., designed two radically
'"/>
Contact: Tom Rickey
trickey@admin.rochester.edu
716-275-7954
University of Rochester
16-Jun-1999