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Researchers identify mechanism of cancer caused by loss of BRCA1 and BRCA2 gene function
Date:4/28/2014

BOSTON Inherited mutations in the BRCA1 or BRCA2 tumor suppressor genes are by far the most frequent contributors to hereditary cancer risk in the human population, often causing breast or ovarian cancer in young women of child-bearing age. Attempts to test the role that the BRCA genes play in regulating a repair process associated with genome duplication have proven frustratingly difficult in living mammalian cells.

Now investigators at Beth Israel Deaconess Medical Center (BIDMC) report a new mechanism by which BRCA gene loss may accelerate cancer-promoting chromosome rearrangements. The new findings explain how the loss of BRCA1 or BRCA2 function impairs homologous recombination (HR), a normally accurate repair process used to fix DNA breaks, and actually stimulates faulty error-prone HR repair.

Described online in the April 28 issue of the journal Nature, the discovery could ultimately provide clinicians with valuable new information to help them ascertain risk and guide patient treatment when faced with BRCA mutations of uncertain significance, and offers a potentially valuable new tool for the development of cancer therapeutics.

"Mutations in the BRCA genes cause breast and ovarian cancers that affect thousands of women throughout the U.S. and around the world, often striking them in the prime of life," says senior author Ralph Scully, MB BS, PhD, a leader in the Breast Cancer Oncology program in BIDMC's Cancer Center and Associate Professor of Medicine at Harvard Medical School. "For almost two decades, scientists have been striving to better understand the tumor suppressor functions of BRCA1 and BRCA2."

Potentially harmful breaks in DNA strands commonly occur during DNA replication, a prerequisite to cell division. These breaks occur when the replication fork that duplicates the genome stalls at sites of DNA damage. If not properly repaired, the breaks can promote genomic instability, leading to cancer and
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Contact: Bonnie Prescott
bprescot@bidcm.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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