NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control
Open accessAbstract
The ability to sense and respond to DNA damage is critical to maintenance of genomic stability and the prevention of cancer. In this study, we employed a genetic screen to identify a gene, NBA1 (new component of the BRCA1 A complex), that is required for resistance to ionizing radiation. The NBA1 protein localizes to sites of DNA damage and is required for G2/M checkpoint control. Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. NBA1 is required to maintain BRE and Abra1 abundance and for the recruitment of BRCA1 to sites of DNA damage. In depth bioinformatics analysis revealed that the BRCA1 A complex bears striking similarities to the 19S proteasome complex. Furthermore, we show that four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability, thus forming a complex that might facilitate the deubiquitinating activity of the deubiquitination enzyme BRCC36 or the E3 ligase activity of the BRCA1/BARD1 ligase. These findings provide a new perspective from which to view the BRCA1 A complex.
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IRIF formation of BRCA1 and Rap80 is diminished in Abraxas-/- MEFs.
“Consistent with the previous notion that Abraxas plays a critical role in the accumulation of BRCA1 to DNA damage sites and formation of the BRCA1-A complex, the IRIF formation of BRCA1 and Rap80 in Abraxas-/- MEF cells were diminished (Figure S1) (Wang and Elledge, 2007; Wang et al., 2009).”
From The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression (2014) · cites this paper as Wang et al., 2009
The BRCA1 A complex, containing Abraxas, NBA1, BRE, BRCC36, and Rap80, mediates recruitment of BRCA1 to DNA double-strand breaks for DNA damage checkpoint regulation and efficient DNA repair.
“The BRCA1 A complex, comprised of Abraxas, and other components, NBA1, BRE, BRCC36, and Rap80, is found to play an important role in mediating the recruitment of BRCA1 to DNA double strand breaks for DNA damage checkpoint regulation and efficient DNA repair.”
From The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression (2014) · cites this paper as Wang et al., 2009
Deletion of the coiled-coil domain in human Abraxas disrupts binding of Abraxas to BRCC36.
“Previously it was shown deletion of the coiled-coil domain in human Abraxas (ΔCC) disrupts the binding of Abraxas to BRCC36 (Wang et al., 2009)”
From The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression (2014) · cites this paper as Wang et al., 2009
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- Authors
- Wang, B., Hurov, K., Hofmann, K., & Elledge, S. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Miltenyi Biotec (Germany) (DE)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-03-04
- Volume
- 23
- Issue
- 6
- Pages
- 729-739
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2661606
- OpenAlex
- W2147344015
- Cited by
- 172
- References
- 44
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 10 · 2018: 4 · 2017: 6 · 2016: 19 · 2015: 10 · 2014: 10 · 2013: 14 · 2012: 19
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Genes & Development (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- Leukemia and Lymphoma Society
- National Institutes of Health
- U.S. Public Health Service (1U19A1067751-01)
- National Cancer Institute (K01CA116275)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- BRCA1-A complex, BRCA1, DNA damage response, ionizing radiation resistance, G2/M checkpoint, genome stability, 19S proteasome, BRCC36, BRe, RAP80, deubiquitination
- MeSH terms
- Deubiquitinating Enzymes, Amino Acid Sequence, Carrier Proteins, Cell Cycle, DNA Damage, DNA Repair, Humans, Lasers, Membrane Proteins, Molecular Sequence Data, BRCA1 Protein, Polyubiquitin, Cell Line, Tumor, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Ubiquitination
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