A significant advance in understanding the physiologic importance of the BRCA1: BARD1 interaction was the finding that the BRCA1: BARD1 heterodimer functions as an E3 ubiquitin ligase and that this ubiquitin ligase activity was abolished by cancer-associated mutations within the BRCA1 RING domain (Brzovic et al., 2001; Hashizume et al., 2001). Here, BRCA1 is linked to cancer.