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

  1. Yi Wang1,2,6,
  2. David Cortez1,3,6,
  3. Parvin Yazdi1,2,
  4. Norma Neff5,
  5. Stephen J. Elledge1,3,4, and
  6. Jun Qin1,2,7
  1. 1Verna and Mars McLean Department of Biochemistry and Molecular Biology, 2Department of Cellular and Molecular Biology, 3Howard Hughes Medical Institute, and 4Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 USA; 5Laboratory of Molecular Genetics, New York Blood Center, New York, New York 10021 USA

Abstract

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 genomesurveillance 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.

Keywords

Footnotes

  • 6 These authors contributed equally.

  • 7 Corresponding author.

  • E-MAIL jqin{at}bcm.tmc.edu; FAX (713) 798-1625.

    • Received January 21, 2000.
    • Accepted March 2, 2000.
| Table of Contents

Life Science Alliance