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 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.
Wang
Y
Y
Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cortez
D
D
Yazdi
P
P
Neff
N
N
Elledge
S J
SJ
Qin
J
J
D000251:Adenosine Triphosphatases / Q000378:metabolism; D019313:BRCA1 Protein / Q000378:metabolism* / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D053484:RecQ Helicases; D051818:Replication Protein C; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014158:Transcription, Genetic
D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C086930:RAD50 protein, S cerevisiae; C497561:RFC2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D051818:Replication Protein C; D053484:RecQ Helicases