Genomic DNA transposition induced by human PGBD5

  1. Anton G Henssen
  2. Elizabeth Henaff
  3. Eileen Jiang
  4. Amy R Eisenberg
  5. Julianne R Carson
  6. Camila M Villasante
  7. Mondira Ray
  8. Eric Still
  9. Melissa Burns
  10. Jorge Gandara
  11. Cedric Feschotte
  12. Christopher E Mason
  13. Alex Kentsis  Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States
  2. Weill Cornell Medical College, United States
  3. Harvard Medical School, United States
  4. University of Utah School of Medicine, United States

Abstract

Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. Here, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vertebrates, can induce stereotypical cut-and-paste DNA transposition in human cells. Genomic integration activity of PGBD5 requires distinct aspartic acid residues in its transposase domain, and specific DNA sequences containing inverted terminal repeats with similarity to piggyBac transposons. DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. The apparent conservation of DNA transposition activity by PGBD5 suggests that genomic remodeling contributes to its biological function.

Article and author information

Author details

  1. Anton G Henssen

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elizabeth Henaff

    Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eileen Jiang

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amy R Eisenberg

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Julianne R Carson

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Camila M Villasante

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Mondira Ray

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Eric Still

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Melissa Burns

    Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Jorge Gandara

    Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Cedric Feschotte

    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Christopher E Mason

    Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Alex Kentsis

    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    kentsisresearchgroup@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Michael R Botchan, University of California, Berkeley, United States

Version history

  1. Received: August 3, 2015
  2. Accepted: September 23, 2015
  3. Accepted Manuscript published: September 25, 2015 (version 1)
  4. Version of Record published: October 29, 2015 (version 2)

Copyright

© 2015, Henssen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Anton G Henssen
  2. Elizabeth Henaff
  3. Eileen Jiang
  4. Amy R Eisenberg
  5. Julianne R Carson
  6. Camila M Villasante
  7. Mondira Ray
  8. Eric Still
  9. Melissa Burns
  10. Jorge Gandara
  11. Cedric Feschotte
  12. Christopher E Mason
  13. Alex Kentsis
(2015)
Genomic DNA transposition induced by human PGBD5
eLife 4:e10565.
https://doi.org/10.7554/eLife.10565

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