DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations

Kevin Hiom, Meni Melek, Martin Gellert (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    441 Citations (Scopus)

    Abstract

    The RAG1 and RAG2 proteins are known to initiate V(D)J recombination by making a double-strand break between the recombination signal sequence (RSS) and the neighboring coding DNA. We show that these proteins can also drive the coupled insertion of cleaved recombination signals into new DNA sites in a transpositional reaction. This RAG-mediated DNA transfer provides strong evidence for the evolution of the V(D)J recombination system from an ancient mobile DNA element and suggests that repeated transposition may have promoted the expansion of the antigen receptor loci. The inappropriate diversion of V(D)J rearrangement to a transpositional pathway may also help to explain certain types of DNA translocation associated with lymphatic tumors.

    Original languageEnglish
    Pages (from-to)463-470
    Number of pages8
    JournalCell
    Volume94
    Issue number4
    DOIs
    Publication statusPublished - 21 Aug 1998

    Keywords

    • DNA
    • DNA Nucleotidyltransferases
    • DNA Transposable Elements
    • DNA-Binding Proteins
    • Evolution, Molecular
    • Gene Rearrangement, T-Lymphocyte
    • Homeodomain Proteins
    • Lymphoma
    • Models, Genetic
    • Nucleotidyltransferases
    • Oncogenes
    • Receptors, Antigen, T-Cell
    • Recombination, Genetic
    • Translocation, Genetic
    • Transposases
    • VDJ Recombinases

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