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http://purl.uniprot.org/citations/12660252http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12660252http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12660252http://www.w3.org/2000/01/rdf-schema#comment"DNA double-strand breaks originating from diverse causes in eukaryotic cells are accompanied by the formation of phosphorylated H2AX (gammaH2AX) foci. Here we show that gammaH2AX formation is also a cellular response to topoisomerase I cleavage complexes known to induce DNA double-strand breaks during replication. In HCT116 human carcinoma cells exposed to the topoisomerase I inhibitor camptothecin, the resulting gammaH2AX formation can be prevented with the phosphatidylinositol 3-OH kinase-related kinase inhibitor wortmannin; however, in contrast to ionizing radiation, only camptothecin-induced gammaH2AX formation can be prevented with the DNA replication inhibitor aphidicolin and enhanced with the checkpoint abrogator 7-hydroxystaurosporine. This gammaH2AX formation is suppressed in ATR (ataxia telangiectasia and Rad3-related) deficient cells and markedly decreased in DNA-dependent protein kinase-deficient cells but is not abrogated in ataxia telangiectasia cells, indicating that ATR and DNA-dependent protein kinase are the kinases primarily involved in gammaH2AX formation at the sites of replication-mediated DNA double-strand breaks. Mre11- and Nbs1-deficient cells are still able to form gammaH2AX. However, H2AX-/-mouse embryonic fibroblasts exposed to camptothecin fail to form Mre11, Rad50, and Nbs1 foci and are hypersensitive to camptothecin. These results demonstrate a conserved gammaH2AX response for double-strand breaks induced by replication fork collision. gammaH2AX foci are required for recruiting repair and checkpoint protein complexes to the replication break sites."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m300198200"xsd:string
http://purl.uniprot.org/citations/12660252http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m300198200"xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Furuta T."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Furuta T."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Takemura H."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Takemura H."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Bonner W.M."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Bonner W.M."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Pilch D.R."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Pilch D.R."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Redon C."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Redon C."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Rogakou E.P."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Rogakou E.P."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Pommier Y."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Pommier Y."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Aladjem M.I."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Aladjem M.I."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Nussenzweig A."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Nussenzweig A."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Chen H.T."xsd:string
http://purl.uniprot.org/citations/12660252http://purl.uniprot.org/core/author"Chen H.T."xsd:string