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Transposition of hAT elements links transposable elements and V(D)J recombination

Nature volume 432, pages 995–1001 (2004)Cite this article

Abstract

Transposons are DNA sequences that encode functions that promote their movement to new locations in the genome. If unregulated, such movement could potentially insert additional DNA into genes, thereby disrupting gene expression and compromising an organism's viability. Transposable elements are classified by their transposition mechanisms and by the transposases that mediate their movement. The mechanism of movement of the eukaryotic hAT superfamily elements was previously unknown, but the divergent sequence of hAT transposases from other elements suggested that these elements might use a distinct mechanism. Here we have analysed transposition of the insect hAT element Hermes in vitro. Like other transposons, Hermes excises from DNA via double-strand breaks between the donor-site DNA and the transposon ends, and the newly exposed transposon ends join to the target DNA. Interestingly, the ends of the donor double-strand breaks form hairpin intermediates, as observed during V(D)J recombination, the process which underlies the combinatorial formation of antigen receptor genes. Significant similarities exist in the catalytic amino acids of Hermes transposase, the V(D)J recombinase RAG, and retroviral integrase superfamily transposases, thereby linking the movement of transposable elements and V(D)J recombination.

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Figure 1: Hermes transposase binds specifically to the ends of Hermes.
Figure 2: Hermes transposition involves hairpin formation on the flanking donor-site DNA.
Figure 3: Hermes transposase joins the 3′ OH end of Hermes-L to a target DNA.
Figure 4: Comparison of recombinase-mediated cleavage and target-joining mechanisms.
Figure 5: Mutation of Hermes DDE residues block DNA cleavage and strand transfer.

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Acknowledgements

We are grateful to G. Chaconas for sharing his thoughts about hairpin binding pockets before publication. N.L.C. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Molecular Biology & Genetics, Johns Hopkins School of Medicine, Baltimore, Maryland, 21205, USA

    Liqin Zhou, Rupak Mitra & Nancy L. Craig

  2. Department of Entomology and Institute for Integrative Genome Biology, University of California, Riverside, California, 92521, USA

    Peter W. Atkinson

  3. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, 20892, USA

    Alison Burgess Hickman & Fred Dyda

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Correspondence to Nancy L. Craig.

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Zhou, L., Mitra, R., Atkinson, P. et al. Transposition of hAT elements links transposable elements and V(D)J recombination. Nature 432, 995–1001 (2004). https://doi.org/10.1038/nature03157

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