Anton Henssen, Elizabeth Henaff, Eileen Jiang, Amy R Eisenberg, Julianne R Carson, Camila Villasante, Mondira Ray, Eric Still, Melissa Burns, Jorge Gandara, Cedric Feschotte, Christopher E. Mason, Alex Kentsis
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.