Our research has contributed to the developing concept of a BRCA1-centered breast and ovarian tumor suppressor network. BRCA1 forms several distinct DNA damage inducible 'supercomplexes,' each dedicated to specific checkpoint and repair activities following genotoxic stress. These studies have provided a framework for understanding the in vivo consequences of mutations within the BRCA1 network (i.e. genes encoding BRCA1-interacting proteins) (Greenberg et al. Genes&Dev 2006). Recent work has revealed a partial molecular understanding for how BRCA1 recognizes DNA damage sites (Sobhian et al., Science 2007). We have demonstrated that an interaction between the BRCA1 BRCT domain and the RAP80 ubiquitin binding protein targets BRCA1 to K63-linked ubiquitin structures present at DNA damage sites. The RAP80 ubiquitin interaction motifs (UIMs) provide an ubiquitin recognition element to target the BRCA1 E3 ligase and a K63-ubiquitin specific deubiquitinating enzyme BRCC36 to DNA double strand breaks. Each of these activities is required for appropriate checkpoint and repair responses to ionizing radiation (Sobhian et al. Science 2007; Shao et al. Genes&Dev 2009; Shao et al. PNAS 2009; Nikkila et al. Oncogene 2009). Cancer causing BRCA1 BRCT mutants fail to interact with RAP80 and consequently demonstrate inefficient recruitment to DNA damage sites. Thus a series of ordered events involving ubiquitin recognition, breakdown and synthesis are required for BRCA1-dependent DNA damage responses. Future work will address the relationship between ubiquitin turnover and BRCA1-dependent DNA repair function. These studies should provide a detailed knowledge of the (1) molecular determinants required for BRCA1 recognition of DNA damage, and (2) how BRCA1 influences DNA repair mechanism specificity. Clinical mutations frequently disrupt these activities, thus understanding the basis for BRCA1 recognition of DNA damage should lend significant new insight into BRCA1 dependent DNA repair and tumor suppression mechanisms.