The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development.
Previous in vitro studies defined the minimal regions of RAG1 and RAG2 essential for V(D)J recombination. In order to characterize the role of the C-terminal "dispensable" portion of RAG2, we generated core-RAG2 knock-in mice. We found that the core-RAG2-containing recombinase complex is selectively defective in catalyzing V-to-DJ rearrangement at the IgH and TCRbeta loci, resulting in partial developmental blocks in B and T lymphopoiesis. Analysis of recombination intermediates showed defects at the cleavage phase of the reaction. We also observed a reduction in overall recombinase activity in core-RAG2-expressing thymocytes, leading us to suggest that the interaction of a defective recombinase with RSS sequences unique to VH and Vbeta gene segments may underlie the specific V-to-DJ rearrangement defect in core-RAG2 mice.
Duke Scholars
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- VDJ Recombinases
- T-Lymphocytes
- Recombination, Genetic
- Mice
- Immunology
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
- Gene Rearrangement, B-Lymphocyte, Heavy Chain
- DNA-Binding Proteins
- DNA Nucleotidyltransferases
- Cell Line
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- VDJ Recombinases
- T-Lymphocytes
- Recombination, Genetic
- Mice
- Immunology
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
- Gene Rearrangement, B-Lymphocyte, Heavy Chain
- DNA-Binding Proteins
- DNA Nucleotidyltransferases
- Cell Line