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Molecular and Cellular Biology, July 2001, p. 4302-4310, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4302-4310.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

RAG Transposase Can Capture and Commit to Target DNA before or after Donor Cleavage

Matthew B. Neiditch,1 Gregory S. Lee,1 Mark A. Landree,2 and David B. Roth1,2,3,*

Department of Immunology,1 Interdepartmental Program in Cell and Molecular Biology,2 and Howard Hughes Medical Institute,3 Baylor College of Medicine, Houston, Texas 77030

Received 16 February 2001/Returned for modification 11 March 2001/Accepted 4 April 2001

The discovery that the V(D)J recombinase functions as a transposase in vitro suggests that transposition by this system might be a potent source of genomic instability. To gain insight into the mechanisms that regulate transposition, we investigated a phenomenon termed target commitment that reflects a functional association between the RAG transposase and the target DNA. We found that the V(D)J recombinase is quite promiscuous, forming productive complexes with target DNA both before and after donor cleavage, and our data indicate that the rate-limiting step for transposition occurs after target capture. Formation of stable target capture complexes depends upon the presence of active-site metal binding residues (the DDE motif), suggesting that active-site amino acids in RAG-1 are critical for target capture. The ability of the RAG transposase to commit to target prior to cleavage may result in a preference for transposition into nearby targets, such as immunoglobulin and T-cell receptor loci. This could bias transposition toward relatively "safe" regions of the genome. A preference for localized transposition may also have influenced the evolution of the antigen receptor loci.

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

Molecular and Cellular Biology, July 2001, p. 4302-4310, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4302-4310.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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