1. Academic Validation
  2. Genomic DNA transposition induced by human PGBD5

Genomic DNA transposition induced by human PGBD5

  • Elife. 2015 Sep 25;4:e10565. doi: 10.7554/eLife.10565.
Anton G Henssen 1 Elizabeth Henaff 2 Eileen Jiang 1 Amy R Eisenberg 1 Julianne R Carson 1 Camila M Villasante 1 Mondira Ray 1 Eric Still 1 Melissa Burns 3 Jorge Gandara 2 Cedric Feschotte 4 Christopher E Mason 2 Alex Kentsis 1 5 6
Affiliations

Affiliations

  • 1 Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
  • 2 Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States.
  • 3 Boston Children's Hospital, Harvard Medical School, Boston, United States.
  • 4 Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States.
  • 5 Department of Pediatrics, Memorial Sloan Kaettering Cancer Center, New York, United States.
  • 6 Weill Cornell Medical College, Cornell University, New York, 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. In this study, 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.

Keywords

DNA transposition; chromosomes; genes; genome remodeling; human; recombination.

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