Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of 
familial breast and ovarian cancer. The BRCA1 protein displays E3 ubiquitin 
ligase activity, and this enzymatic function is thought to be required for tumor 
suppression. To test this hypothesis, we generated mice that express an 
enzymatically defective Brca1. We found that this mutant Brca1 prevents tumor 
formation to the same degree as does wild-type Brca1 in three different 
genetically engineered mouse (GEM) models of cancer. In contrast, a mutation 
that ablates phosphoprotein recognition by the BRCA C terminus (BRCT) domains of 
BRCA1 elicits tumors in each of the three GEM models. Thus, BRCT phosphoprotein 
recognition, but not the E3 ligase activity, is required for BRCA1 tumor 
suppression.