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Cell. 2008 Dec 12;135(6):1028-38. doi: 10.1016/j.cell.2008.09.062.

AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

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.

PMID:
19070574
PMCID:
PMC2713603
DOI:
10.1016/j.cell.2008.09.062
[Indexed for MEDLINE]
Free PMC Article

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