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DNA mutation rates raise curtain on cause of cancer
Date:7/1/2010

utation rates increase, and the types of mutation during repair are different from normal mutagenesis, explained Hicks, the lead author. "It would be interesting to do an in depth analysis of the types of mutations in cancer cells and compare to those we observed in a repair event to see if they match up."

While other studies have looked at GCs and mutation rates in the past, this is the first study to look directly at the region where both DNA strands are replaced. The researchers used yeast cells, a simple organism in which it is possible to induce a single DSB at one location in all cells and then count the number of mutations that arise during the repair of the break. Through this simple system, Haber and his colleagues were able not only to measure the mutation rates, but also to determine which DNA repair enzymes are most important for GC, and to suggest a possible reason for the high number of mutations created.

They discovered that an innate repair system known as mismatch repair does not get recruited during GC; therefore mutations cannot be fixed. In addition, they discovered that many of the repair-associated mutations had a distinct "signature", which suggested that the copying of DNA that must occur during the repair of the break was frequently interrupted and required a way to "find the right place" to recommence copying. One striking consequence of the lack of straightforward copying was that some of the repair events involved "template switches," in which the copying machinery jumped from the template it was supposed to use to another, distantly related DNA sequence on another chromosome.

"The next steps for this project will be to better characterize these template switches we observed," said Hicks. "What is the actual rate of these events? What proteins are required or not to do the template switches?"

It will now be important to see if there is an acceleration of mutagenesis in precancerous mammalian cells a
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Contact: Laura Gardner
gardner@brandeis.edu
781-736-4204
Brandeis University
Source:Eurekalert

Page: 1 2 3

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