title: Genomic DNA transposition induced by human PGBD5.
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.
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Anton G
authors.initials: AG
authors.lastname: Henssen
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States.
authors.forename: Elizabeth
authors.identifier: http://orcid.org/0000-0001-7906-9681
authors.initials: E
authors.lastname: Henaff
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Eileen
authors.initials: E
authors.lastname: Jiang
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Eisenberg
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Julianne R
authors.initials: JR
authors.lastname: Carson
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Villasante
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Mondira
authors.initials: M
authors.lastname: Ray
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Still
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Burns
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gandara
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Cedric
authors.initials: C
authors.lastname: Feschotte
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.affiliation: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, United States.|Department of Pediatrics, Memorial Sloan Kaettering Cancer Center, New York, United States.|Weill Cornell Medical College, Cornell University, New York, United States.
authors.forename: Alex
authors.identifier: http://orcid.org/0000-0002-8063-9191
authors.initials: A
authors.lastname: Kentsis
mesh_terms: D004251:DNA Transposable Elements; D006801:Humans; D011995:Recombination, Genetic; D013379:Substrate Specificity; D019895:Transposases / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; C000608604:PGBD5 protein, human; D019895:Transposases
keywords: DNA transposition; chromosomes; genes; genome remodeling; human; recombination