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

By Yi Wang, D. Cortez, P. Yazdi, N. Neff, Stephen J. Elledge, J. Qin. Genes & Development, 2000

1,294 citations recorded by the source corpus.

We report the identities of the members of a group of proteins that associate with BRCA1 to form a large complex that we have named BASC (BRCA1-associated genome surveillance complex). This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex. In addition, DNA replication factor C (RFC), a protein complex that facilitates the loading of PCNA onto DNA, is also part of BASC. We find that BRCA1, the BLM helicase, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci that contain PCNA when cells are treated with agents that interfere with DNA synthesis. The association of BRCA1 with MSH2 and MSH6, which are required for transcription-coupled repair, provides a possible explanation for the role of BRCA1 in this pathway. Strikingly, 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-associated repair. Collectively, these results suggest that BRCA1 may function as a coordinator of multiple activities required for maintenance of genomic integrity during the process of DNA replication and point to a central role for BRCA1 in DNA repair.

Subfields: Genetics, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/0f02e259c098981876d837784c1b3735e7acbc9f

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Citations in the corpus

Systematic discovery of in vivo phosphorylation networks. (2007, background): “The latter reﬂects the knowledge that ATM interacts with the MRN complex and copuriﬁes with Rad50 as part of the BASC supercomplex (Wang et al., 2000), a sensor of DNA damage.”
Apoptosis and Molecular Targeting Therapy in Cancer (2014, background): “Recently, BRCA1 has been found to reside in a large DNA repair complex that includes various mismatch repair proteins including hMLH1 and hMSH2; thus, it plays a role in DNA repair [208].”
Mechanisms of human DNA repair: an update. (2003, background): “Several DNA-damage repair proteins such as BRCA1, MSH2, MSH6, MLH1, ATM, BLM, and the RAD50–MRE11–NBS1 complex , can be co-immunoprecipitated in the so called BRCA1-associated surveillance complex, named BASC (Wang et al., 2000a).”