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Genomic DNA transposition induced by human PGBD5

Anton G. Henssen, Elizabeth Henaff, Eileen Jiang, Amy R. Eisenberg, Julianne R. Carson, Camila M. Villasante, Mondira Ray, Eric Still, Melissa Burns, Jorge Gandara, Cedric Feschotte, Christopher E. Mason, Alex Kentsis
doi: https://doi.org/10.1101/023887
Anton G. Henssen
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Elizabeth Henaff
bInstitute for Computational Biomedicine, Weill Cornell Medical College, New York, NY
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Eileen Jiang
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Amy R. Eisenberg
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Julianne R. Carson
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Camila M. Villasante
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Mondira Ray
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Eric Still
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
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Melissa Burns
cBoston Children’s Hospital, Boston, MA
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Jorge Gandara
bInstitute for Computational Biomedicine, Weill Cornell Medical College, New York, NY
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Cedric Feschotte
dDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT
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Christopher E. Mason
bInstitute for Computational Biomedicine, Weill Cornell Medical College, New York, NY
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Alex Kentsis
aMolecular Pharmacology Program, Sloan Kettering Institute, New York, NY
eDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY 10065
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  • For correspondence: kentsisresearchgroup@gmail.com
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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 chordates, 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 with 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 raises the possibility that genomic remodeling may contribute to its biological function.

Footnotes

  • The authors declare no conflict of interest.

  • Data deposition: The data reported in this manuscript have been deposited to the Sequence Read Archive (SRA), http://www.ncbi.nlm.nih.gov/sra/ (accession number SRP061649).

  • This article contains supporting information online.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 03, 2015.
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Genomic DNA transposition induced by human PGBD5
Anton G. Henssen, Elizabeth Henaff, Eileen Jiang, Amy R. Eisenberg, Julianne R. Carson, Camila M. Villasante, Mondira Ray, Eric Still, Melissa Burns, Jorge Gandara, Cedric Feschotte, Christopher E. Mason, Alex Kentsis
bioRxiv 023887; doi: https://doi.org/10.1101/023887
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Genomic DNA transposition induced by human PGBD5
Anton G. Henssen, Elizabeth Henaff, Eileen Jiang, Amy R. Eisenberg, Julianne R. Carson, Camila M. Villasante, Mondira Ray, Eric Still, Melissa Burns, Jorge Gandara, Cedric Feschotte, Christopher E. Mason, Alex Kentsis
bioRxiv 023887; doi: https://doi.org/10.1101/023887

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