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Inner Workings of Gene Tied to Breast, Ovarian Cancer Revealed
Date:8/23/2010

o bump off those cells so they can't divide and behave badly."

Under normal circumstances, the BRCA gene would automatically correct those problems.

"But if you have certain mutations in the BRCA gene, then one of the mechanisms of repair - the BRCA gene - is not functioning properly, so that cell is allowed to proliferate and grow out of control," Smith said.

Over the course of several, often frustrating years, these scientists were able to purify the protein, which consists of 3,418 amino acids, to reveal some of its inner workings.

As it turns out, BRCA2 binds with another protein, RAD51, in a specific way to make sure that any breaks in the DNA get fixed correctly.

"It's a basic science discovery but it has many implications," said Stephen Kowalczykowski, senior author of the paper appearing in Nature and distinguished professor of microbiology and molecular and cellular biology at the University of California, Davis. "One would be that since we now know how the protein works, we can try to screen for therapeutic agents that could mitigate some of these problems."

"This illuminates a function of BRCA2 that's going to give new ideas to people who are involved in translational [lab-to-bedside] work," added Dr. Priscilla A. Furth, a professor of oncology and medicine at Lombardi Cancer Center of Georgetown University in Washington, D.C. "This is good, solid, basic science that is going to put us on a firm ground as we now look at why we get cancers from the loss of BRCA2."

"The more we can understand where the defect is the more we can try to correct it. RAD51 could be a molecule that we could target to make DNA repair actually effective in BRCA patients," Smith added. "That's the import of this work. It's not going to help us right now but we're moving more and more towards targeted therapy, designing treatments that target specific molecular abnormalities."

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