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Key function of mutation in hereditary breast and ovarian cancer gene discovered
Date:9/1/2011

Richmond, Va. (September 1, 2011) It is widely known that mutations in the breast cancer susceptibility 1 (BRCA1) gene significantly increase the chance of developing breast and ovarian cancers, but the mechanisms at play are not fully understood. Now, researchers at Virginia Commonwealth University Massey Cancer Center have shown that certain BRCA1 mutations result in excessive, uncontrolled DNA repair, which challenges the prior assumption that mutations in BRCA1 only contribute to breast cancer through a reduction in function.

Recently published in the journal Aging, the study led by Kristoffer Valerie, Ph.D., discovered that certain BRCA1 mutations affecting the BRCA1 C-terminal (BRCT) binding site resulted in excessive DNA repair, or hyper-recombination, which may contribute to the development of breast and ovarian cancers. The BRCT domain is a protein binding site typically found on DNA repair proteins like BRCA1 that are responsible for maintaining genomic stability and facilitating DNA repair. This study has implications for the treatment, diagnosis and development of therapies for patients with breast and ovarian cancer.

"Our findings suggest that caution should be exercised when targeting BRCA1 for breast and ovarian cancer therapies," says Valerie, co-leader of the Radiation Biology and Oncology program and a professor in the Department of Radiation Oncology at VCU Massey Cancer Center. "We need to better understand the biological mechanisms that lead to the development of breast and ovarian cancer before we attempt to attack it through targeted therapies aimed at causing DNA damage."

When DNA damage occurs, various forms of BASC (BRCA1-associated genome surveillance complex) bind to the BRCT domain on BRCA1. BASC is a protein complex that in part binds to the BRCT domain and serves as a "docking site" for other proteins and enzymes to come in, effectively repair the DNA damage and leave when repair is completed. Howeve
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Contact: John Wallace
wallacej@vcu.edu
804-628-1550
Virginia Commonwealth University
Source:Eurekalert

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