| http://purl.uniprot.org/citations/25751062 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25751062 | http://www.w3.org/2000/01/rdf-schema#comment | "The Fanconi anemia/BRCA (FA/BRCA) pathway is a DNA repair pathway that is required for excision of DNA interstrand cross-links. The 17 known FA proteins, along with several FA-associated proteins (FAAPs), cooperate in this pathway to detect, unhook, and excise DNA cross-links and to subsequently repair the double-strand breaks generated in the process. In the current study, we identified a patient with FA with a point mutation in FANCA, which encodes a mutant FANCA protein (FANCAI939S). FANCAI939S failed to bind to the FAAP20 subunit of the FA core complex, leading to decreased stability. Loss of FAAP20 binding exposed a SUMOylation site on FANCA at amino acid residue K921, resulting in E2 SUMO-conjugating enzyme UBC9-mediated SUMOylation, RING finger protein 4-mediated (RNF4-mediated) polyubiquitination, and proteasome-mediated degradation of FANCA. Mutation of the SUMOylation site of FANCA rescued the expression of the mutant protein. Wild-type FANCA was also subject to SUMOylation, RNF4-mediated polyubiquitination, and degradation, suggesting that regulated release of FAAP20 from FANCA is a critical step in the normal FA pathway. Consistent with this model, cells lacking RNF4 exhibited interstrand cross-linker hypersensitivity, and the gene encoding RNF4 was epistatic with the other genes encoding members of the FA/BRCA pathway. Together, the results from our study underscore the importance of analyzing unique patient-derived mutations for dissecting complex DNA repair processes."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci79325"xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "D'Andrea A.D."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Kim H."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Takeda S."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Xie J."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Moreau L.A."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Garber J."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Al Abo M."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/author | "Puhalla S."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/pages | "1523-1532"xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/title | "RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway."xsd:string |
| http://purl.uniprot.org/citations/25751062 | http://purl.uniprot.org/core/volume | "125"xsd:string |
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| http://purl.uniprot.org/citations/25751062 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25751062 |
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