BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures
AUTOR(ES)
Wang, Yi
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=316544Documentos Relacionados
- BRCA1-associated growth arrest is RB-dependent
- The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations
- Preclinical mouse models for BRCA1-associated breast cancer
- Vimentin and laminin expression is associated with basal‐like phenotype in both sporadic and BRCA1‐associated breast carcinomas
- Integrin β3 Leu33Pro polymorphism increases BRCA1‐associated ovarian cancer risk