Navigation Links
Key function of mutation in hereditary breast and ovarian cancer gene discovered

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. However, certain BRCT mutants unable to bind to BASC disrupt the delicate DNA repair process. Previously, it was assumed this meant that BRCA1 was unable to assist with the repair process and, thus, recombination did not occur.

Valerie and his colleagues showed through experiments with cultured breast cancer cells and tissue samples from breast cancer patients that BRCT mutants increased ubiquination of BASC, which, in turn, increased recombination several-fold over normal levels. Ubiquitin is a small protein in all living organisms that "marks" other proteins for degradation or, as more recently discovered, the participation in specific cellular processes such as recombination. The researchers proposed that the hyper-recombination resulting from increased ubiquination of the BASC might result in improperly repaired DNA and increased genomic instability, which could lead to the development and aggressive progression of breast and ovarian cancers.

"Our results point to ubiquitination as a potential therapeutic target," says Valerie. "By disrupting ubiquitination we may be able to prevent hyper-recombination and stop the growth of cancer cells with these BRCT mutations. This might sensitize the cancer cells to radiation therapy while having little effect on cells with normal BRCA1 function."

The researchers hope to continue studying the role of BRCA1 in DNA double-strand break repair in order to determine whether the mutations they examined are important for the onset of cancer and whether targeted therapies can be developed.


Contact: John Wallace
Virginia Commonwealth University

Related medicine news :

1. Common Heart Dysfunction Can Help Bring on Heart Failure
2. When erectile dysfunction isnt whole story
3. New piece to the puzzle of brain function
4. Medical Tattoo Tracks Body Functions
5. With Age, Focus on Body Shifts From Appearance to Function
6. Neighborhood status influences older womens cognitive function, study finds
7. Antioxidants of growing interest to address infertility, erectile dysfunction
8. Drug improves brain function in condition that leads to Alzheimers
9. Exposure to Common Chemicals May Affect Thyroid Function
10. Stem cell treatment may restore cognitive function in patients with brain cancer
11. New brain research suggests eating disorders impact brain function
Post Your Comments:
(Date:6/26/2016)... ... June 26, 2016 , ... Pixel Film Studios Released ProSlice ... "Film editors can give their videos a whole new perspective by using the ... of Pixel Film Studios. , ProSlice Levels contains over 30 Different presets to ...
(Date:6/26/2016)... Birmingham, Lake Orion, Clarkston, Michigan (PRWEB) , ... ... ... their direction with respect to fertility once they have been diagnosed with endometriosis. ... for tolerable intercourse but they also require a comprehensive approach that can help ...
(Date:6/25/2016)... Miami, FL (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton ... Plant City Observer , brings up a new, often overlooked aspect of head lice: ... The closing for fumigation is not a common occurrence, but a necessary one in the ...
(Date:6/25/2016)... Beach, CA (PRWEB) , ... June 25, 2016 , ... ... UCLA with Magna Cum Laude and his M.D from the David Geffen School of ... Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at the ...
(Date:6/25/2016)... ... 25, 2016 , ... Conventional wisdom preaches the benefits of moderation, whether it’s ... setting the bar too high can result in disappointment, perhaps even self-loathing. However, those ... goal. , Research from reveals that behind the tendency to ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... Story Highlights: ... the health care industry is causing providers to review ... Deloitte offers a suite of solutions for health care ... cost optimization: labor resource analysis, revenue cycle optimization and ... outcomes and better economics ...
(Date:6/24/2016)... June 24, 2016  Collagen Matrix, Inc., ("Collagen ... and manufacturing of collagen and mineral based medical ... that Bill Messer has joined the ... further leverage the growing portfolio of oral surgery, ... Bill joins the Collagen Matrix executive team ...
(Date:6/24/2016)...   Bay Area Lyme Foundation , collaborating ... for Tick Borne Illness , Harvard Medical School ... Medicine, University of California, Berkeley, and the Veterans ... finalists of Lyme Innovation , the first ... scientists, clinicians, researchers, entrepreneurs, and investors from several ...
Breaking Medicine Technology: