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It is estimated that 200,000 new incidences of breast cancer will be diagnosed in the U.S. in 2002. For women with a family history of the disease, about half of the cases will be caused by mutations in one of two genes: BRCA1 and BRCA2. Now findings published online by the journal Science reveal the crystal structure of the BRCA2 protein and demonstrate how mutations in the gene could contribute to tumor growth.
Previous research had suggested that BRCA2 was involved in DNA repair, but its mechanism remained unclear. "By studying the normal function of BRCA2, we can understand how changes in the protein contribute to the development of cancer," explains Nikola P. Pavletich of the Memorial Sloan-Kettering Cancer Center, a co-author of the study. Using a process known as x-ray crystallography, Haijuan Yang of Cornell University and colleagues assembled a three-dimensional picture of BRCA2 (see image). The team determined that the protein can bind to broken DNA and--through a process known as homologous recombination--fix "double-strand" breaks in which both parts of the DNA double helix incur damage at the same time. When this first-aid kit fails, the researchers posit, the faulty DNA can lead to tumor growth in the breast, ovaries, prostate and pancreas.
John H. Wilson and Stephen J. Elledge of the Baylor College of Medicine write in an accompanying editorial that the study "marks an important milestone in BRCA2 research." But they caution that "although profound, the insights into BRCA2 provided by Yang and colleagues do not solve the classic mystery of why BRCA2 mutations lead to tumors in such a well-defined subset of human tissues."