A key step in understanding the origins of familial breast cancer has been made by two teams of scientists at the University of California, Davis. The researchers have purified, for the first time, the protein produced by the breast cancer susceptibility gene BRCA2 and used it to study the oncogene's role in DNA repair.
The results will be published online Aug. 22 in the journals Nature, and Nature Structural and Molecular Biology. They open new possibilities for understanding, diagnosing and perhaps treating breast cancer.
BRCA2 is known to be involved in repairing damaged DNA, but exactly how it works with other molecules to repair DNA has been unclear, said Stephen Kowalczykowski, distinguished professor of microbiology in the UC Davis College of Biological Sciences, UC Davis Cancer Center member and senior author of the Nature paper.
"Having the purified protein makes possible far more detailed studies of how it works," Kowalczykowski said.
Kowalczykowski's group has purified the protein from human cells; another group led by Professor Wolf-Dietrich Heyer, also in the UC Davis Department of Microbiology and leader of the Cancer Center's molecular oncology program, used genetic engineering techniques to manufacture the human protein in yeast. That work is published in Nature Structural and Molecular Biology.
The two approaches are complementary, Heyer said, and the two teams have been talking and cooperating throughout.
"It's nice to be able to compare the two and see no disagreements between the results," Heyer said.
Experiments with the BRCA2 protein confirm that it plays a role in repairing damaged DNA. It acts as a mediator, helping another protein, RAD51, to associate with a single strand of DNA and stimulating its activity. One BRCA2 molecule can bind up to six molecules of RAD51.
The RAD51/DNA complex then looks for the matching strand o
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University of California - Davis - Health System