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Molecular and Cellular Biology, August 2005, p. 6475-6484, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6475-6484.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Both V(D)J Coding Ends but Neither Signal End Can Recombine at the bcl-2 Major Breakpoint Region, and the Rejoining Is Ligase IV Dependent

Sathees C. Raghavan,1 Chih-Lin Hsieh,2,3 and Michael R. Lieber1*

Departments of Pathology, Biochemistry and Molecular Biology, Molecular Microbiology and Immunology, and Biological Sciences,1 Department of Urology,2 Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Ave., Rm. 5428, Los Angeles, California 90089-91763

Received 24 February 2005/ Returned for modification 31 March 2005/ Accepted 13 April 2005

The t(14;18) chromosomal translocation is the most common translocation in human cancer, and it occurs in all follicular lymphomas. The 150-bp bcl-2 major breakpoint region (Mbr) on chromosome 18 is a fragile site, because it adopts a non-B DNA conformation that can be cleaved by the RAG complex. The non-B DNA structure and the chromosomal translocation can be recapitulated on intracellular human minichromosomes where immunoglobulin 12- and 23-signals are positioned downstream of the bcl-2 Mbr. Here we show that either of the two coding ends in these V(D)J recombination reactions can recombine with either of the two broken ends of the bcl-2 Mbr but that neither signal end can recombine with the Mbr. Moreover, we show that the rejoining is fully dependent on DNA ligase IV, indicating that the rejoining phase relies on the nonhomologous DNA end-joining pathway. These results permit us to formulate a complete model for the order and types of cleavage and rejoining events in the t(14;18) translocation.

* Corresponding author. Mailing address: USC Norris Comprehensive Cancer Ctr., Rm. 5428, 1441 Eastlake Ave., Los Angeles, CA 90089-9176. Phone: (323) 865-0568. Fax: (323) 865-3019. E-mail: lieber{at}usc.edu.

Molecular and Cellular Biology, August 2005, p. 6475-6484, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6475-6484.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lieber, M. R., Raghavan, S. C., Yu, K. (2008). Mechanistic Aspects of Lymphoid Chromosomal Translocations. J Natl Cancer Inst Monogr 2008: 8-11 [Abstract] [Full Text]  


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