Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells
Baker, Richard E.
Ucher, Anna J.
Guikema, Jeroen E. J.
UMass Chan AffiliationsDepartment of Microbiology and Physiological Systems
KeywordsAmino Acid Motifs
*DNA Breaks, Double-Stranded
Immunoglobulin Class Switching
Repetitive Sequences, Nucleic Acid
Genetics and Genomics
Immunology and Infectious Disease
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AbstractAfter immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen-binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading to antibody class switch recombination (CSR). We asked if, during B cell activation, AID also induces DNA breaks at genes other than IgH genes. Using a nonbiased genome-wide approach, we have identified hundreds of reproducible, AID-dependent DSBs in mouse splenic B cells shortly after induction of CSR in culture. Most interestingly, AID induces DSBs at sites syntenic with sites of translocations, deletions, and amplifications found in human B cell lymphomas, including within the oncogene B cell lymphoma11a (bcl11a)/evi9. Unlike AID-induced DSBs in Ig genes, genome-wide AID-dependent DSBs are not restricted to transcribed regions and frequently occur within repeated sequence elements, including CA repeats, non-CA tandem repeats, and SINEs.
Mol Cell. 2011 Jan 21;41(2):232-42. doi: 10.1016/j.molcel.2011.01.007. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/36509
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