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Molecular and Cellular Biology, April 2002, p. 2068-2077, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.2068-2077.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Targeted Transposition by the V(D)J Recombinase

Gregory S. Lee,1 Matthew B. Neiditch,1 Richard R. Sinden,2 and David B. Roth1,3*

Department of Immunology,1 Howard Hughes Medical Institute, Baylor College of Medicine,3 Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, Texas 770302

Received 4 October 2001/ Returned for modification 30 November 2001/ Accepted 4 January 2002

Cleavage by the V(D)J recombinase at a pair of recombination signal sequences creates two coding ends and two signal ends. The RAG proteins can integrate these signal ends, without sequence specificity, into an unrelated target DNA molecule. Here we demonstrate that such transposition events are greatly stimulated by—and specifically targeted to—hairpins and other distorted DNA structures. The mechanism of target selection by the RAG proteins thus appears to involve recognition of distorted DNA. These data also suggest a novel mechanism for the formation of alternative recombination products termed hybrid joints, in which a signal end is joined to a hairpin coding end. We suggest that hybrid joints may arise by transposition in vivo and propose a new model to account for some recurrent chromosome translocations found in human lymphomas. According to this model, transposition can join antigen receptor loci to partner sites that lack recombination signal sequence elements but bear particular structural features. The RAG proteins are capable of mediating all necessary breakage and joining events on both partner chromosomes; thus, the V(D)J recombinase may be far more culpable for oncogenic translocations than has been suspected.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030. Phone: (713) 798-8145. Fax: (512) 857-0178. E-mail: davidbr{at}bcm.tmc.edu.

Molecular and Cellular Biology, April 2002, p. 2068-2077, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.2068-2077.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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