Biologists have discovered the first of a new DNA polymerase family: a last-gasp enzyme that yeast cells turn to when all attempts to fix damaged DNA have failed. The enzyme increases a cell's odds at staying alive, but it does so by dramatically boosting the type of mutations that, in humans and other animals, sometimes become the genetic seeds from which cancers grow. The research by the University of Rochester team, done by creating in yeast the type of damage that sunlight does to our own DNA, is reported in the June 14 issue of Science.
The findings shed new light on how yeast and probably other organisms cope with damaged DNA, a constant, potentially dangerous problem for yeast and humans alike. Damaged DNA that is copied to other cells carries a much greater risk of causing cancer and other diseases than healthy DNA does. By copying damaged DNA, the new enzyme serves as a fountain of mutations; corking it would be one way to prevent damaged DNA from propagating and to squelch genetic mishaps before they develop into full-blown disease.
The enzyme, dubbed "zeta," is a member of the first new eukaryotic DNA polymerase family to be discovered in about a decade and is the first polymerase whose purpose is to allow an organism to tolerate, rather than fix or discard, damaged DNA. Unlike other polymerases, which either refuse to copy damaged DNA or which help repair it, zeta lets a cell replicate damaged DNA, giving the cell a chance at life at the cost of a higher mutation rate for the organism.
"Replicating past the damaged site is the least
favored mechanism of dealing with DNA damage, but from the cell's perspective, it's better to replicate damaged DNA and
survive than to not replicate and die," says Christopher Lawrence, professor of biophysics. Working with Lawrence on the
project, funded by the National Institutes of Health, are research associate John Nelson in the Department o
Contact: Tom Rickey
University of Rochester