title: Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination.
abstract: Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-mediated cassette exchange, we established a cell line-based CSR assay that allows manipulation of switch sequences at the endogenous locus. We show that AGCT is only one of a family of four WGCW motifs in the switch region that can facilitate CSR. We go on to show that it is the overlap of AID hotspots at WGCW sites on the top and bottom strands that is critical. This finding leads to a much clearer model for the difference between CSR and somatic hypermutation.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Masani
authors.forename: Kefei
authors.initials: K
authors.lastname: Yu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003564:Cytidine Deaminase / Q000276:immunology* / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011995:Recombination, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase