BRCA1 supercomplex formation in response to DNA damage. BRCA1 acts in many cellular supercomplexes and executes distinct roles. BARD1 stoichiometrically interacts with BRCA1 and exists as a RING heterodimer in all the complexes shown, indicating the importance of E3 ligase activity in each complex. (a) BRCA1-BARD1 in the Pol II-holoenzyme may act as a transcriptional co-activator. In addition, BRCA1 that interacts with hyperphosphorylated Pol II acts as a sensor for DNA damage. After some types of DNA damage, BRCA1 dissociates with Pol II. BRCA1-BARD1 may polyubiquitinate subunits of this complex at this time, including the hyperphosphorylated largest subunit (RPB1) and the common small subunit (RPB8). (b) BRCA1 that interacts with BACH1/BRIP1/FANCJ at its C-terminus locates the replication point with BARD1. This complex interacts with TopBP1 in an ATM dependent manner after DNA damage and causes TopBP1 dissociation from the replication point. This results in the failure to recruit the replication initiation factor Cdc45, likely engaging the intra S-phase checkpoint. (c) Mre11-Rad50-Nbs1 also forms a complex with BRCA1-BARD1 at sites of DNA damage. This BRCA1 complex interacts with CtIP via the BRCA1 C-terminus. Complex formation depends on ATM- and Chk2-mediated phosphorylation. This complex signals the G2/M checkpoint and bridges the two DNA ends of the DSB, an intermediate of both non-homologous end joining (NHEJ) and homologous recombination (HR). (d) BRCA1 constitutes S-phase nuclear foci with BARD1, Rad51 and BRCA2. After DNA damage, these once disperse foci again localize to damaged DNA sites. BRCA1 is necessary for recruiting these proteins. This complex is important for homologous recombination repair of DSB. (e) BRCA1-BARD1 is targeted to polyubiquitin chains at DNA damaged sites through BRCT domain-interacting phosphorylated ABRA1 that interacts with UIM containing protein RAP80.