There have been hints of a previously unknown polymerase in yeast, but only with recent technology could Nelson, working with Hinkle and Lawrence, prove it by purifying the enzyme and demonstrating its function.
Mutant yeast without the enzyme are slightly more likely to die than their zeta-carrying counterparts, but they're also far less likely to suffer detrimental mutations. Indeed, yeast that lack one of the two genes that code for the enzyme have only about 5 percent as many mutations as "normal" yeast.
Mutations are a risk wherever there is damaged DNA -- and damaged DNA is an unavoidable fact of life. It comes not only from cigarettes, sunlight, and other factors, but also happens naturally and constantly as the body's cells replicate the seven-foot strand of DNA that's in all our cells.
More than 99 percent of DNA damage in our bodies is fixed by special repair enzymes. But sometimes these repair enzymes can't keep up with the damage, or the damage is so severe that even the body's internal editors can't fix it before replication occurs.
Unrepaired damage usually stymies polymerases, which normally zip along a section of DNA, copying nucleotides uneventfully and assembling new strands of DNA. Zeta, however, is at least 10 times more efficient at getting around these impasses, somehow replicating past unrepaired sites. This keeps the cell alive, but it increases the odds of a mutation.
"This is a last-gasp system," says Hinkle. "For the cell, it's better to mutate than to die."
Lawrence believes that this process accounts for 2/3 to 3/4 of all spontaneous mutations in yeast, including base
substitutions, the type often seen in cancer cells or oncogenes like p53 or ras in humans. His laboratory
is now searching for counterparts in humans to the two genes that code for zeta, and scientist Peter Gibbs has found one
whose sequence
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Contact: Tom Rickey
trickey@admin.rochester.edu
716-275-7954
University of Rochester
14-Jun-1996