| http://purl.uniprot.org/citations/19402749 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19402749 | http://www.w3.org/2000/01/rdf-schema#comment | "5-Fluorouracil (5-FU), a chemotherapeutic drug commonly used in cancer treatment, imbalances nucleotide pools, thereby favoring misincorporation of uracil and 5-FU into genomic DNA. The processing of these bases by DNA repair activities was proposed to cause DNA-directed cytotoxicity, but the underlying mechanisms have not been resolved. In this study, we investigated a possible role of thymine DNA glycosylase (TDG), one of four mammalian uracil DNA glycosylases (UDGs), in the cellular response to 5-FU. Using genetic and biochemical tools, we found that inactivation of TDG significantly increases resistance of both mouse and human cancer cells towards 5-FU. We show that excision of DNA-incorporated 5-FU by TDG generates persistent DNA strand breaks, delays S-phase progression, and activates DNA damage signaling, and that the repair of 5-FU-induced DNA strand breaks is more efficient in the absence of TDG. Hence, excision of 5-FU by TDG, but not by other UDGs (UNG2 and SMUG1), prevents efficient downstream processing of the repair intermediate, thereby mediating DNA-directed cytotoxicity. The status of TDG expression in a cancer is therefore likely to determine its response to 5-FU-based chemotherapy."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pbio.1000091"xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Saito Y."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Focke F."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Kunz C."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Schuermann D."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Schar P."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Lettieri T."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/author | "Selfridge J."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/name | "PLoS Biol"xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/pages | "e91"xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/title | "Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil."xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/19402749 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19402749 |
| http://purl.uniprot.org/citations/19402749 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19402749 |
| http://purl.uniprot.org/uniprot/#_P56581-mappedCitation-19402749 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19402749 |
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| http://purl.uniprot.org/uniprot/#_H3BLR1-mappedCitation-19402749 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19402749 |
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| http://purl.uniprot.org/uniprot/#_Q3TLR4-mappedCitation-19402749 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19402749 |
| http://purl.uniprot.org/uniprot/#_Q9Z1T3-mappedCitation-19402749 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19402749 |
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