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Location Key for Breast Cancer Protein

Keeping BRCA1 out of cell nucleus may enhance the killing power of radiation or the chemotherapy drug

September 17, 2010 | Leigh MacMillan

Mutations in the BRCA1 gene have been implicated in the development of inherited breast cancers. The BRCA1 protein participates in processes including repair of DNA breaks, DNA replication, and cell death. BRCA1 moves between the cell nucleus and cytoplasm, and Fen Xia, M.D., Ph.D., and colleagues have proposed that active “shuttling” between cellular compartments may regulate BRCA1’s functions.

The researchers report in the Aug. 1 issue of Cancer Research that BRCA1 must be in the nucleus to repair DNA breaks. They found that confining BRCA1 to the cytoplasm of human breast and colon cancer cells enhanced the cytotoxicity (killing power) of radiation or the chemotherapy drug cisplatin. This enhanced cytotoxicity depended on the shuttling of BRCA1 to the cytoplasm, but not on its DNA repair activities.

The findings suggest a novel role for BRCA1 nuclear/cytoplasmic shuttling in the regulation of cell death processes following DNA damage. BRCA1 shuttling may provide a marker to predict tumor response and a novel target to sensitize cancer cells to DNA damage-based therapies.

For other research highlights from Vanderbilt University Medical Center laboratories, see ‘Aliquots‘ in the VUMC Reporter.