Salvage Gene Is At The Root Of Many Mutations

A trio of University of Rochester researchers has unexpectedly discovered that most mutations in yeast are caused by the activity of an enzyme that acts to salvage irreparably damaged DNA. The enzyme, REV1, helps a cell evade its own stringent quality control and opens the door to mutations. The findings are reported in the August 22 issue of Nature.

The researchers set out to understand the function of a family of DNA repair enzymes in yeast. When they damaged the yeast's DNA and then studied the yeast's coping mechanisms, they made a startling discovery: Almost all mutations in DNA, ironically, result from the activity of one of the DNA repair enzymes, REV1.

"We really found something that we weren't at all looking for," says David Hinkle, associate professor of biology. "This was a bombshell." Also working on the project, funded by the National Institutes of Health, are postdoctoral fellow John Nelson and Christopher Lawrence, professor of biophysics.

The vast majority of mutations come not from asbestos, pesticides, or other environmental factors, but from normal chemistry that goes on within our bodies. "DNA is not a stainless steel molecule," Lawrence points out. "It is susceptible to damage as a natural part of its existence."

The most common form of DNA damage is sporadic loss of individual molecules of adenine and guanine -- two of the four bases that encode genetic information along a strand of DNA. Such losses result in genetic gaps known as "abasic" sites.

"Formation of these abasic sites," says Hinkle, "is, in fact, one of the most common occurrences in our cells," taking place every day in about 10,000 to 20,000 of the three trillion DNA bases in each of our cells. Uncorrected abasic sit

Contact: Steve Bradt
University of Rochester

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