AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations.
Cell
; 135(6): 1028-38, 2008 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-19070574
ABSTRACT
Chromosomal 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
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Genes myc
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Citidina Desaminase
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Genes de Cadeia Pesada de Imunoglobulina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article