ArticleNucleic acids research2014
Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- FANCI: from genome guardian to translational therapeutic target.Frontiers in oncology · 2026Review
- Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex.The Journal of clinical investigation · 2025Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Article
- Identification of small-molecule binding sites of a ubiquitin-conjugating enzyme-UBE2T through fragment-based screening.Protein science : a publication of the Protein Society · 2024Article
- The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export.Cell reports · 2024Article
- Phosphorylation by ATR triggers FANCD2 chromatin loading and activates the Fanconi anemia pathway.Cell reports · 2023Article
- Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.The EMBO journal · 2023Article
- Fanconi anemia: current insights regarding epidemiology, cancer, and DNA repair.Human genetics · 2022Review
- HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.Cell death & disease · 2022Article
- Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory, high-grade serous ovarian cancer.Cell reports. Medicine · 2021Article
- Focal Point of Fanconi Anemia Signaling.International journal of molecular sciences · 2021Review
- Synthesis of DNA Duplexes Containing Site-Specific Interstrand Cross-Links via Sequential Reductive Amination Reactions Involving Diamine Linkers and Abasic Sites on Complementary Oligodeoxynucleotides.Chemical research in toxicology · 2021Article
- Regulation of the Fanconi Anemia DNA Repair Pathway by Phosphorylation and Monoubiquitination.Genes · 2021Review
- Promyelocytic Leukemia Proteins Regulate Fanconi Anemia Gene Expression.International journal of molecular sciences · 2021Article
- Identification of Biomarkers Based on Bioinformatics Analysis: The Expression of Ubiquitin-Conjugating Enzyme E2T (UBE2T) in the Carcinogenesis and Progression of Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Structure of the FA core ubiquitin ligase closing the ID clamp on DNA.Nature structural & molecular biology · 2021Article
- Formation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA.DNA repair · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
FANCD2 and FANCI function together in the Fanconi anemia network of deoxyribonucleic acid (DNA) crosslink repair. These proteins form the dimeric ID2 complex that binds DNA and becomes monoubiquitinated upon exposure of cells to DNA crosslinking agents. The monoubiquitinated ID2 complex is thought to facilitate DNA repair via recruitment of specific nucleases, translesion DNA polymerases and the homologous recombination machinery. Using the ubiquitin conjugating enzyme (E2) UBE2T and ubiquitin ligase (E3) FANCL, monoubiquitination of human FANCD2 and FANCI was examined. The ID2 complex is a poor substrate for monoubiquitination, consistent with the published crystal structure showing the solvent inaccessibility of the target lysines. Importantly, FANCD2 monoubiquitination within the ID2 complex is strongly stimulated by duplex or branched DNA, but unstructured single-stranded DNA or chromatinized DNA is ineffective. Interaction of FANCL with the ID2 complex is indispensable for its E3 ligase efficacy. Interestingly, mutations in FANCI that impair its DNA binding activity compromise DNA-stimulated FANCD2 monoubiquitination. Moreover, we demonstrate that in the absence of FANCD2, DNA also stimulates FANCI monoubiquitination, but in a FANCL-independent manner. These results implicate the role of a proper DNA ligand in FANCD2 and FANCI monoubiquitination, and reveal regulatory mechanisms that are dependent on protein-protein and protein-DNA interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.