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  • The EMBO Journal (2002) 21, 6625 - 6633
  • doi:10.1093/emboj/cdf630

Inverse transposition by the RAG1 and RAG2 proteins: role reversal of donor and target DNA

I-hung Shih1,3, Meni Melek2,3, Nadeesha D. Jayaratne1 and Martin Gellert1

  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 241, Bethesda, MD 20892, USA
  2. Present address: Salamandra, LLC, 4600 North Park Avenue, Suite 100, Chevy Chase, MD 20815, USA
  3. I-h.Shih and M.Melek contributed equally to this work

Correspondence to:

Martin Gellert, E-mail: gellert@helix.nih.gov

Received 18 July 2002; Accepted 2 October 2002; Revised 24 September 2002

The lymphoid-specific proteins RAG1 and RAG2 initiate V(D)J recombination by introducing DNA double-strand breaks at the recombination signal sequences (RSSs). In addition to DNA cleavage, the versatile RAG1/2 complex is capable of catalyzing several other reactions, including hybrid joint formation and the transposition of signal ends into a second DNA. Here we show that the RAG1/2 complex also mediates an unusual strand transfer reaction, inverse transposition, in which non-RSS DNA is cleaved and subsequently transferred to an RSS sequence by direct transesterification. Characterization of the reaction products and requirements suggests that inverse transposition is related to both hybrid joint formation and signal-end transposition. This aberrant activity provides another possible mechanism for some chromosomal translocations present in lymphoid tumors.

  • Keywords:

    • chromosomal translocation,
    • RAG1/2,
    • recombinase,
    • transposition,
    • V(D)J recombination