| http://purl.uniprot.org/citations/28819025 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28819025 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypomorphic mutations in the genes encoding the MRE11/RAD50/NBS1 (MRN) DNA repair complex lead to cancer-prone syndromes. MRN binds DNA double-strand breaks, where it functions in repair and triggers cell-cycle checkpoints via activation of the ataxia-telangiectasia mutated kinase. To gain understanding of MRN in cancer, we engineered mice with B lymphocytes lacking MRN, or harboring MRN in which MRE11 lacks nuclease activities. Both forms of MRN deficiency led to hallmarks of cancer, including oncogenic translocations involving c-Myc and the immunoglobulin locus. These preneoplastic B lymphocytes did not progress to detectable B lineage lymphoma, even in the absence of p53. Moreover, Mre11 deficiencies prevented tumorigenesis in a mouse model strongly predisposed to spontaneous B-cell lymphomas. Our findings indicate that MRN cannot be considered a standard tumor suppressor and instead imply that nuclease activities of MRE11 are required for oncogenesis. Inhibition of MRE11 nuclease activity increased DNA damage and selectively induced apoptosis in cells overexpressing oncogenes, suggesting MRE11 serves an important role in countering oncogene-induced replication stress. Thus, MRE11 may offer a target for cancer therapeutic development. More broadly, our work supports the idea that subtle enhancements of endogenous genome instability can exceed the tolerance of cancer cells and be exploited for therapeutic ends. Cancer Res; 77(19); 5327-38. ©2017 AACR."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-17-1355"xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Smith C.J."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Morgan M.J."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Sekiguchi J.M."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Ferguson D.O."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Buis J."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Dinkelmann M."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Spehalski E."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/author | "Capper K.M."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/pages | "5327-5338"xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/title | "MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress."xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://purl.uniprot.org/core/volume | "77"xsd:string |
| http://purl.uniprot.org/citations/28819025 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28819025 |
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