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    Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells

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    Authors
    Staszewski, Ori
    Baker, Richard E.
    Ucher, Anna J.
    Martier, Raygene
    Stavnezer, Janet
    Guikema, Jeroen E. J.
    UMass Chan Affiliations
    Department of Microbiology and Physiological Systems
    Document Type
    Journal Article
    Publication Date
    2011-01-21
    Keywords
    Amino Acid Motifs
    Animals
    B-Lymphocytes
    Binding Sites
    Carrier Proteins
    Cytidine Deaminase
    *DNA Breaks, Double-Stranded
    Genes, myc
    Immunoglobulin Class Switching
    Lymphocyte Activation
    Mice
    Nuclear Proteins
    Repetitive Sequences, Nucleic Acid
    Genetics and Genomics
    Immunology and Infectious Disease
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044441/pdf/nihms264188.pdf
    Abstract
    After 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.
    Source

    Mol Cell. 2011 Jan 21;41(2):232-42. doi: 10.1016/j.molcel.2011.01.007. Link to article on publisher's site

    DOI
    10.1016/j.molcel.2011.01.007
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/36509
    PubMed ID
    21255732
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.molcel.2011.01.007
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