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Molecular and Cellular Biology, August 2004, p. 6850-6860, Vol. 24, No. 15
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.15.6850-6860.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

DNA Cleavage Activity of the V(D)J Recombination Protein RAG1 Is Autoregulated

Pallabi De, Mandy M. Peak, and Karla K. Rodgers*

Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190

Received 7 August 2003/ Returned for modification 7 October 2003/ Accepted 12 May 2004

RAG1 and RAG2 catalyze the first DNA cleavage steps in V(D)J recombination. We demonstrate that the isolated central domain of RAG1 has inherent single-stranded (ss) DNA cleavage activity, which does not require, but is enhanced by, RAG2. The central domain, therefore, contains the active-site residues necessary to perform hydrolysis of the DNA phosphodiester backbone. Furthermore, the catalytic activity of this domain on ss DNA is abolished by addition of the C-terminal domain of RAG1. The inhibitory effects of this latter domain are suppressed on substrates containing double-stranded (ds) DNA. Together, the activities of the reconstituted domains on ss versus mixed ds-ss DNA approximate the activity of intact RAG1 in the presence of RAG2. We propose how the combined actions of the RAG1 domains may function in V(D)J recombination and also in aberrant cleavage reactions that may lead to genomic instability in B and T lymphocytes.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190. Phone: (405) 271-2227, ext. 1248. Fax: (405) 271-3139. E-mail: karla-rodgers{at}ouhsc.edu.

Molecular and Cellular Biology, August 2004, p. 6850-6860, Vol. 24, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.15.6850-6860.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Simkus, C., Anand, P., Bhattacharyya, A., Jones, J. M. (2007). Biochemical and Folding Defects in a RAG1 Variant Associated with Omenn Syndrome. J. Immunol. 179: 8332-8340 [Abstract] [Full Text]  
  • Rahman, N. S., Godderz, L. J., Stray, S. J., Capra, J. D., Rodgers, K. K. (2006). DNA Cleavage of a Cryptic Recombination Signal Sequence by RAG1 and RAG2: IMPLICATIONS FOR PARTIAL VH GENE REPLACEMENT. J. Biol. Chem. 281: 12370-12380 [Abstract] [Full Text]  


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