Nature Structural Biology pp 833 - 837 and pp 838 - 842

Breast cancer is one of the most common and deadly forms of cancer in women. In the U.S. alone, ~18,000 women are diagnosed annually. One of the risk factors for this disease is mutation in the tumor suppressor protein BRCA1. Mutations in BRCA1 are linked to the familial and early onset forms of breast cancer and affect ~5% of the patients suffering from this disease. These mutations often occur in the N- and C-terminal regions of BRCA1, which are essential for its function.

BRCA1 is involved in a variety of cellular processes, such as DNA repair, and appears to be important in maintaining genome integrity. While scientists are beginning to understand the cellular functions of BRCA1, the molecular basis for the mutations that predispose women for breast cancer is not clear. To address this deficiency, two groups of researchers report in this issue of Nature Structural Biology the high-resolution structures of the N- and C-terminal regions of BRCA1.

In one paper, Rachel Klevit and coworkers at the University of Washington at Seatle, USA, describe the solution structure of the N-terminal region of BRCA1, called the RING domain, in complex with the RING domain from a BRCA1-associated protein called BARD1. In the second paper, Mark Glover and colleagues of the University of Alberta at Edmonton, Canada, report the crystal structure of the C-terminal region of BRCA1 called the BRCT repeat. The locations of the cancer-predisposing mutations within these structures suggest that the mutations may affect the architecture of the domains and thus compromise the tumor-suppressing activities of BRCA1. Richard Baer of the Columbia University discusses these findings in an associated News and Views.