BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures

We report the identities of the members of a group of proteins that associa te with BRCA1 to form a large complex that we have named BASC (BRCA1-associ ated genome Surveillance complex). This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MR E11-NBS1 protein complex. In addition, DNA replication factor C (RFC), a pr otein complex that facilitates the loading of PCNA onto DNA, is also part o f BASC. We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 comp lex colocalize to large nuclear foci that contain PCNA when cells are treat ed with agents that interfere with DNA synthesis. The association of BRCA1 with MSH2 and MSH6, which are required for transcription-coupled repair, pr ovides a possible explanation for the role of BRCA1 in this pathway. Striki ngly, all members of this complex have roles in recognition of abnormal DNA structures or damaged DNA, suggesting that BASC may serve as a sensor for DNA damage. Several of these proteins also have roles in DNA replication-as sociated repair. Collectively, these results suggest that BRCA1 may functio n as a coordinator of multiple activities required for maintenance of genom ic integrity during the process of DNA replication and point to a central r ole for BRCA1 in DNA repair.