Navigation Links
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. 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
wallacej@vcu.edu
804-628-1550
Virginia Commonwealth University
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... ... legally blind and certified personal trainer is helping to develop a weight loss fitness plan ... fix the two major problems leading the fitness industry today:, , ... They don’t eliminate all the reasons people quit their exercise program ...
(Date:6/25/2016)... TX (PRWEB) , ... June 25, 2016 , ... Austin ... of the American College of Mohs Surgery and to Dr. Russell Peckham for medical ... and highly effective treatment for skin cancer. The selective fellowship in Mohs Micrographic Surgery ...
(Date:6/25/2016)... TX (PRWEB) , ... June 25, 2016 , ... ... the United States, named Dr. Sesan Ogunleye, as the Medical Director of its new ... the facility Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, ... Bronze Wellness at Work award to iHire in recognition of their exemplary accomplishments in ... the 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott in ...
(Date:6/24/2016)... ... ... Those who have experienced traumatic events may suffer from a complex set ... drug or alcohol abuse, as a coping mechanism. To avoid this pain and suffering, ... traumatic event. , Trauma sufferers tend to feel a range of emotions, from depression, ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Consumers have ... and regulators/payers have placed more emphasis on patient ... patient support programs in the pharmaceutical industry have ... medications. Consequently, pharmaceutical companies are focusing on becoming ... are providing products and services that improve health. ...
(Date:6/24/2016)... , June 24, 2016 ... the "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" ... In-Mold Electronics, Smart Skin, Structural ... Structural electronics involves electronic and/or ... protective structures, replacing dumb structures such as vehicle ...
(Date:6/24/2016)... , June 24, 2016 According ... by Type (Standard Pen Needles, Safety Pen Needles), Needle ... GLP-1, Growth Hormone), Mode of Purchase (Retail, Non-Retail) - ... This report studies the market for the forecast period ... reach USD 2.81 Billion by 2021 from USD 1.65 ...
Breaking Medicine Technology: