AID Is Required for the Chromosomal Breaks in c-myc that Lead to c-myc/IgH Translocations
| Autor: | Simone Difilippantonio, Hua Tang Chen, Michel C. Nussenzweig, Elsa Callen, Anne E. Corcoran, Daniel J. Bolland, Bernardo Reina-San-Martin, Davide F. Robbiani, Anne Bothmer, André Nussenzweig, Yair Dorsett |
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| Rok vydání: | 2008 |
| Předmět: |
DNA damage
Genes Immunoglobulin Heavy Chain Genes myc HUMDISEASE Somatic hypermutation Chromosomal translocation Biology Translocation Genetic General Biochemistry Genetics and Molecular Biology Article Mice chemistry.chemical_compound immune system diseases Cytidine Deaminase hemic and lymphatic diseases Animals Humans DNA Breaks Double-Stranded MOLIMMUNO Embryonic Stem Cells B-Lymphocytes Integrases Biochemistry Genetics and Molecular Biology(all) Promoter Cytidine deaminase Burkitt Lymphoma Molecular biology Mice Inbred C57BL chemistry Immunoglobulin class switching Immunoglobulin heavy chain CELLBIO DNA Plasmacytoma |
| Zdroj: | Cell. 135(6):1028-1038 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2008.09.062 |
| Popis: | SummaryChromosomal translocation requires formation of paired double-strand DNA breaks (DSBs) on heterologous chromosomes. One of the most well characterized oncogenic translocations juxtaposes c-myc and the immunoglobulin heavy-chain locus (IgH) and is found in Burkitt's lymphomas in humans and plasmacytomas in mice. DNA breaks in IgH leading to c-myc/IgH translocations are created by activation-induced cytidine deaminase (AID) during antibody class switch recombination or somatic hypermutation. However, the source of DNA breaks at c-myc is not known. Here, we provide evidence for the c-myc promoter region being required in targeting AID-mediated DNA damage to produce DSBs in c-myc that lead to c-myc/IgH translocations in primary B lymphocytes. Thus, in addition to producing somatic mutations and DNA breaks in antibody genes, AID is also responsible for the DNA lesions in oncogenes that are required for their translocation. |
| Databáze: | OpenAIRE |
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