ArticleMutation research2010
Several tetratricopeptide repeat (TPR) motifs of FANCG are required for assembly of the BRCA2/D1-D2-G-X3 complex, FANCD2 monoubiquitylation and phleomycin resistance.
Article in Mutation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Molecular architecture of meiotic pro-crossover factor HEI10 reveals coupling of higher-order assembly and ubiquitin chain formation.bioRxiv : the preprint server for biology · 2026Article
- Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- Identification of a HypomorphicGenes · 2022Article
- Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant inInternational journal of molecular sciences · 2022Article
- Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.Molecular and cellular biology · 2020Article
- Role of RUNX Family Transcription Factors in DNA Damage Response.Molecules and cells · 2020Review
- The functional importance of lamins, actin, myosin, spectrin and the LINC complex in DNA repair.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Fanconi anaemia and cancer: an intricate relationship.Nature reviews. Cancer · 2018Review
- Nuclear alpha spectrin: Critical roles in DNA interstrand cross-link repair and genomic stability.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity.Seminars in radiation oncology · 2015Review
- FANCD2, FANCJ and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex.Cell cycle (Georgetown, Tex.) · 2015Article
- Review
- Article
- Functional and physical interaction between the mismatch repair and FA-BRCA pathways.Human molecular genetics · 2011Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The Fanconi anaemia (FA) FANCG protein is an integral component of the FA nuclear core complex that is required for monoubiquitylation of FANCD2. FANCG is also part of another protein complex termed D1-D2-G-X3 that contains FANCD2 and the homologous recombination repair proteins BRCA2 (FANCD1) and XRCC3. Formation of the D1-D2-G-X3 complex is mediated by serine-7 phosphorylation of FANCG and occurs independently of the FA core complex and FANCD2 monoubiquitylation. FANCG contains seven tetratricopeptide repeat (TPR) motifs that mediate protein-protein interactions and here we show that mutation of several of the TPR motifs at a conserved consensus residue ablates the in vivo binding activity of FANCG. Expression of mutated TPR1, TPR2, TPR5 and TPR6 in Chinese hamster fancg mutant NM3 fails to functionally complement its hypersensitivities to mitomycin C (MMC) and phleomycin and fails to restore FANCD2 monoubiquitylation. Using co-immunoprecipitation analysis, we demonstrate that these TPR-mutated FANCG proteins fail to interact with BRCA2, XRCC3, FANCA or FANCF. The interactions of other proteins in the D1-D2-G-X3 complex are also absent, including the interaction of BRCA2 with both the monoubiquitylated (FANCD2-L) and non-ubiquitylated (FANCD2-S) isoforms of FANCD2. Interestingly, a mutation of TPR7 (R563E), that complements the MMC and phleomycin hypersensitivity of human FA-G EUFA316 cells, fails to complement NM3, despite the mutated FANCG protein co-precipitating with FANCA, BRCA2 and XRCC3. Whilst interaction of TPR7-mutated FANCG with FANCF does appear to be reduced in NM3, FANCD2 is monoubiquitylated suggesting that sub-optimal interactions of FANCG in the core complex and the D1-D2-G-X3 complex are responsible for the observed MMC- and phleomycin-hypersensitivity, rather than a defect in FANCD2 monoubiquitylation. Our data demonstrate that FANCG functions as a mediator of protein-protein interactions and is vital for the assembly of multi-protein complexes including the FA core complex and the D1-D2-G-X3 complex.
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