| http://purl.uniprot.org/citations/18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18515798 | http://www.w3.org/2000/01/rdf-schema#comment | "Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g. oxidatively damaged DNA, UV-irradiated DNA, alkylated DNA, uracil-substituted DNA, mismatched DNA, gapped and nicked DNA, and DNA with abasic sites). Top1 cleavage complexes arrest transcription and trigger transcription-dependent degradation of Top1, a phenomenon termed Top1 down-regulation. In the current study, we have investigated the role of Top1 down-regulation in the repair of Top1 cleavage complexes. Using quiescent (serum-starved) human WI-38 cells, camptothecin (CPT) was shown to induce Top1 down-regulation, which paralleled the induction of DNA single-strand breaks (SSBs) (assayed by comet assays) and ATM autophosphorylation (at Ser-1981). Interestingly, Top1 down-regulation, induction of DNA SSBs and ATM autophosphorylation were all abolished by the proteasome inhibitor MG132. Furthermore, studies using immunoprecipitation and dominant-negative ubiquitin mutants have suggested a specific requirement for the assembly of Lys-48-linked polyubiquitin chains for CPT-induced Top1 down-regulation. In contrast to the effect of proteasome inhibition, inactivation of PARP1 was shown to increase the amount of CPT-induced SSBs and the level of ATM autophosphorylation. Together, these results support a model in which Top1 cleavage complexes arrest transcription and activate a ubiquitin-proteasome pathway leading to the degradation of Top1 cleavage complexes. Degradation of Top1 cleavage complexes results in the exposure of Top1-concealed SSBs for repair through a PARP1-dependent process."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m803493200"xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/author | "Ban Y."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/author | "Lin C.P."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/author | "Liu L.F."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/author | "Lyu Y.L."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/author | "Desai S.D."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/pages | "21074-21083"xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/title | "A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes."xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://purl.uniprot.org/core/volume | "283"xsd:string |
| http://purl.uniprot.org/citations/18515798 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18515798 |
| http://purl.uniprot.org/citations/18515798 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18515798 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YVX0-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YX03-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_A0A0A6YY63-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_P11103-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_B9EG90-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_Q3U868-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_Q3ULF5-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_Q3TX36-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_Q921K2-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |
| http://purl.uniprot.org/uniprot/#_Q3UJ03-mappedCitation-18515798 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18515798 |