Open AccessOverlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination
Author(s) -
Li Han,
Shahnaz Masani,
Kefei Yu
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1018726108
Subject(s) - somatic hypermutation , cytidine deaminase , activation induced (cytidine) deaminase , immunoglobulin class switching , biology , genetics , gene conversion , recombinase , sequence motif , site specific recombination , cytidine , gene , recombination , microbiology and biotechnology , enzyme , biochemistry , antibody , b cell
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.