Cited by 1,221DNA Repair MechanismsBRCA gene mutations in cancerPARP inhibition in cancer therapy

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

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Wang, Yi, Cortez, David, Yazdi, Parvin, Neff, Norma, Elledge, Stephen J., Qin, Jun·2000·Genes & Development

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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 (B RCA1-a ssociated genome s urveillance c omplex). 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.

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Authors: Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., & Qin, J.
Affiliations: New York Blood Center (US)
ORCID: Wang, Yi
Cortez, David
Neff, Norma
Elledge, Stephen J.
Qin, Jun
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2000-04-15
Volume: 14
Issue: 8
Pages: 927-939
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.14.8.927
PMC: PMC316544
OpenAlex: W2127566231
Cited by: 1,221
References: 54
Citations by year: 2026: 5 · 2025: 7 · 2024: 10 · 2023: 16 · 2022: 21 · 2021: 27 · 2020: 20 · 2019: 26 · 2018: 20 · 2017: 24 · 2016: 29 · 2015: 33 · 2014: 49 · 2013: 43 · 2012: 35
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
Jane Coffin Childs Memorial Fund for Medical Research
U.S. Bureau of Land Management
U.S. Public Health Service (Q1187)
National Institute of General Medical Sciences (GM-44664, R37GM044664, R01GM044664)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords: BRCA1, BASC, DNA repair, MSH2, MSH6, MLH1, ATM, BLM helicase, PCNA, DNA damage recognition, genome stability, tumor suppressor proteins, nuclear foci
MeSH terms: Adenosine Triphosphatases, Cell Cycle, Cell Nucleus, DNA Repair, DNA Helicases, DNA-Binding Proteins, Endodeoxyribonucleases, Exodeoxyribonucleases, Fluorescent Antibody Technique, Fungal Proteins, HeLa Cells, Humans, Nuclear Proteins, Precipitin Tests, Protein Binding, Mass Spectrometry, Transcription, Genetic, Signal Transduction, Cell Cycle Proteins, BRCA1 Protein, Saccharomyces cerevisiae Proteins, Replication Protein C, RecQ Helicases

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

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