Abstract

The breast and ovarian cancer predisposition protein BRCA1 and its partner, BARD1, have enzymatic activity as a ubiquitin ligase. However whether this has relevance to DNA repair and thus to treatment choice and potentially to cancer predisposition has been unclear. Here we identify a novel element required for activity in a structural subset of dimeric RING ubiquitin ligases including BRCA1:BARD1. Using mutants to separate the role of the heterodimer from that of its activity we demonstrate the role of the activity in DNA repair. Our data indicates substrates of the activity and indicate the mechanistic influence of both mimics of modified substrates and of the ligase activity. Our data support the notion that the enzymatic function of BRCA1 has a role in DNA repair and is likely to be relevant to treatment choice and to cancer predisposition.