Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2
Department of Molecular Genetics and Microbiology
Animals; Antibody Diversity; DNA Primers; DNA-Binding Proteins; Immunoglobulin Class Switching; Immunoglobulin Switch Region; Mice; Mice, Knockout; *Models, Genetic; MutS Homolog 2 Protein; Polymerase Chain Reaction; Proto-Oncogene Proteins; Tandem Repeat Sequences
Life Sciences | Medicine and Health Sciences | Women's Studies
The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem repeat region. We propose that Msh2 affects S site location because sequences with few activation-induced cytidine deaminase targets generate mostly switch DNA cleavages that require Msh2-directed processing to allow CSR joining.
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Citation: J Exp Med. 2005 Jun 20;201(12):1885-90. Epub 2005 Jun 13. Link to article on publisher's site