Sci. STKE, 28 October 2003
CANCER Risk Factors in Breast and Ovarian Cancer
Mutations in breast cancer gene 1 (BRCA1) are a major cause of familial breast cancer. The BRCA1 protein functions in cellular responses to DNA damage, but its precise molecular actions are not fully understood. Two different approaches now show that the C-terminal domain of BRCA1 (BRCT), which is also found in other proteins that function in control of DNA damage, specifically binds to target sequences when serine or threonine residues in the target domain are phosphorylated. Yu et al. (see the Perspective by Caldecott) demonstrate the phosphorylation-dependent interaction of BRCA1 with BRCA1-associated C-terminal helicase and show that this interaction is required for a proper cellular response to DNA damage. Manke et al. used a proteomic strategy to identify BRCT domains in a screen for modules that would bind sequences preferentially phosphorylated by the phosphoinositide-like kinases ATM and ATR, which are activated in response to DNA damage.
Citation: Risk Factors in Breast and Ovarian Cancer. Sci. STKE 2003, tw421 (2003).
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