Published online 24 August 2004
Nucleic Acids Research, Vol. 32 No. 15 © Oxford University Press 2004; all rights reserved
Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice
Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan and 1 Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, CBR Institute for Biomedical Research, Boston, MA 02115, USA
* To whom correspondence should be addressed. Tel: +1 510 574 1609; Fax: +1 510 574 1500; Email: yakamatsu{at}pdl.com
Present address: Yoshiko Akamatsu, Protein Design labs, Inc., 34801 Campus Drive, Fremont, CA 94555, USA
Received May 13, 2004; Revised and Accepted July 30, 2004
RAG1 and RAG2 play a central role in V(D)J recombination, a process for antigen receptor gene assembly. The truncated ‘core’ regions of RAGs are sufficient to catalyze the recombination reaction, although with lower joining efficiency than full-length proteins. To investigate the role of the non-core regions of RAGs in the end-joining phase of antigen receptor rearrangement, we analyzed recombination products isolated from core RAG1 and core RAG2 knock-in mice. Here, we report that the truncation of RAGs increases the frequency of aberrant recombination in vivo. Signal joints (SJs) associated with V-to-D recombination of core RAG1 knock-in mice were normal, whereas those of core RAG2 knock-in mice were highly imprecise, containing large deletions and additions, and in some cases coding sequences. In contrast, we found an elevated level of imprecise D-to-J associated SJs for both core RAG1- and RAG2-expressing mice. Likewise, sequences of coding joints (CJs) were also affected by the expression of core RAGs. Finally, sequences found at the junctions of rearranged T-cell receptor loci were highly influenced by differences in rearranging recombination signal sequence pairs. We provide the first evidence that the non-core regions of RAGs have critical functions in the proper assembly and resolution of recombination intermediates in endogenous antigen receptor loci.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Raval, A. N. Kriatchko, S. Kumar, and P. C. Swanson Evidence for Ku70/Ku80 association with full-length RAG1 Nucleic Acids Res., April 1, 2008; 36(6): 2060 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Simkus, P. Anand, A. Bhattacharyya, and J. M. Jones Biochemical and Folding Defects in a RAG1 Variant Associated with Omenn Syndrome J. Immunol., December 15, 2007; 179(12): 8332 - 8340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chatterji, C.-L. Tsai, and D. G. Schatz Mobilization of RAG-Generated Signal Ends by Transposition and Insertion In Vivo Mol. Cell. Biol., February 15, 2006; 26(4): 1558 - 1568. [Abstract] [Full Text] [PDF]
|
|