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    Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination

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    Authors
    Schrader, Carol E.
    Bradley, Sean P.
    Vardo, Joycelyn
    Mochegova, Sofia N.
    Flanagan, Erin
    Stavnezer, Janet
    UMass Chan Affiliations
    Department of Molecular Genetics and Microbiology
    Document Type
    Journal Article
    Publication Date
    2003-11-01
    Keywords
    Animals
    B-Lymphocytes
    Base Composition
    Base Sequence
    DNA
    DNA Nucleotidylexotransferase
    DNA Repair
    *DNA-Binding Proteins
    *Immunoglobulin Switch Region
    Lymphocyte Activation
    Mice
    Mice, Knockout
    Mice, Transgenic
    Molecular Sequence Data
    MutS Homolog 2 Protein
    *Mutation
    Proto-Oncogene Proteins
    Recombinant Proteins
    *Recombination, Genetic
    Life Sciences
    Medicine and Health Sciences
    Women's Studies
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC275407/
    Abstract
    Nucleotide substitutions are found in recombined Ig switch (S) regions and also in unrecombined (germline, GL) Smicro segments in activated splenic B cells. Herein we examine whether mutations are also introduced into the downstream acceptor S regions prior to switch recombination, but find very few mutations in GL Sgamma3 and Sgamma1 regions in activated B cells. These data suggest that switch recombination initiates in the Smicro segment and secondarily involves the downstream acceptor S region. Furthermore, the pattern and specificity of mutations in GL and recombined Smicro segments differ, suggesting different repair mechanisms. Mutations in recombined Smicro regions show a strong bias toward G/C base pairs and WRCY/RGYW hotspots, whereas mutations introduced into the GL Smicro do not. Additionally, induction conditions affect mutation specificity within the GL Smicro segment. Mutations are most frequent near the S-S junctions and decrease rapidly with distance from the junction. Finally, we find that mice expressing a transgene for terminal deoxynucleotidyl transferase (TdT) have nucleotide insertions at S-S junctions, indicating that the recombining DNA ends are accessible to end-processing enzyme activities.
    Source

    EMBO J. 2003 Nov 3;22(21):5893-903. Link to article on publisher's site

    DOI
    10.1093/emboj/cdg550
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50653
    PubMed ID
    14592986
    Related Resources

    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1093/emboj/cdg550
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