BRCA1-independent ubiquitination of FANCD2
Open accessAbstract
Monoubiquitination of the FANCD2 protein is a key step in the Fanconi anemia (FA) tumor suppressor pathway, coinciding with this molecule's accumulation at sites of genome damage. Strong circumstantial evidence points to a requirement for the BRCA1 gene product in this step. Here, we show that the purified BRCA1/BARD1 complex, together with E1 and UbcH5a, is sufficient to reconstitute the monoubiquitination of FANCD2 in vitro. Although siRNA-mediated knockdown of BRCA1 in human cells results in defective targeting of FANCD2 to sites of DNA damage, it does not lead to a defect in FANCD2 ubiquitination. Furthermore, ablation of the RING finger domains of either BRCA1 or BARD1 in the chicken B cell line DT40 also leaves FANCD2 modification intact. Consequently, while BRCA1 affects the accumulation of FANCD2 at sites of DNA damage, BRCA1/BARD1 E3 ligase activity is not essential for the monoubiquitination of FANCD2.
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BRCA1 interacts with FancD2 and mediates FancD2 foci formation after mitomycin C treatment.
“Since BRCA1 interacts with FancD2 and mediates FancD2 foci formation after treatment with MMC (Bunting et al., 2012; Garcia-Higuera et al., 2001; Vandenberg et al., 2003)”
From The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression (2014) · cites this paper as Vandenberg et al., 2003
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The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression
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- Authors
- Vandenberg, C. J., Gergely, F., Ong, C. Y., Pace, P., Mallery, D. L., Hiom, K., & Patel, K. J.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Hiom, Kevin
- Patel, Ketan J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 12
- Issue
- 1
- Pages
- 247-254
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2017896723
- Cited by
- 131
- References
- 16
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 10 · 2013: 6 · 2012: 5
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- FANCD2, monoubiquitination, BRCA1, BARD1, Fanconi anemia pathway, DNA damage response, RING domain, UbcH5a, E1 ubiquitin-activating enzyme
- MeSH terms
- Animals, Carrier Proteins, Cell-Free System, DNA Damage, Fanconi Anemia, HeLa Cells, Humans, Ligases, Mutation, Nuclear Proteins, Gene Expression Regulation, Neoplastic, Protein Structure, Tertiary, BRCA1 Protein, Tumor Suppressor Proteins, Ubiquitin, Iron-Binding Proteins, RNA, Small Interfering, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Fanconi Anemia Complementation Group D2 Protein
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