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

Waltham, MAWhat if we could understand why cancer develops? We know that certain risk factors, such as smoking or excessive sun exposure, can increase the chances of developing this terrible disease, but cancer can form in any tissue, and the cause is not always clear. One idea that has emerged is that for a cell to transform into a cancer cell it must suffer a large number of mutations affecting different genes needed to control cell growth. In a study published this week in Science, Brandeis University researchers have found that the process of repairing DNA damage also unexpectedly increases the rate of mutations and changes the kinds of mutations that arise.

Surprisingly, as cells progress toward full-blown cancer they begin to suffer alterations of the normal DNA replication process, leading to an increased amount of DNA damage, especially chromosome breaks. Thus there is an increased need for cells to accurately repair these breaks.

Biologist James Haber, graduate student Wade Hicks and undergraduate Minlee Kim report that the repair of damaged strands of DNA, specifically by a process known as gene conversion, can cause higher-than-normal levels of mutation; in fact, 1,400 times as high as spontaneous mutations in cells.

"It has been hard to imagine how cells could accumulate so many mutations in the few generations that they undergo cell division on the way to becoming cancerous," Haber said. "We think that the elevated rate of mutation at sites where DNA has been broken may be an important source of these gene changes."

Most DNA damage takes the form of double-stranded DNA breaks (DSBs), for which the cell has multiple methods of self-repair. One method, gene conversion (GC), was originally believed to be relatively error-free, since it involves repairing the break by copying in DNA from a nearly identical sequence that serves as a library to restore the original DNA sequence.

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Contact: Laura Gardner
gardner@brandeis.edu
781-736-4204
Brandeis University
Source:Eurekalert

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