title: Functional characterization of the human mariner transposon Hsmar2.
abstract: DNA transposons are mobile elements with the ability to mobilize and transport genetic information between different chromosomal loci. Unfortunately, most transposons copies are currently inactivated, little is known about mariner elements in humans despite their role in the evolution of the human genome, even though the Hsmar2 transposon is associated to hotspots for homologous recombination involved in human genetic disorders as Charcot-Marie-Tooth, Prader-Willi/Angelman, and Williams syndromes. This manuscript describes the functional characterization of the human HSMAR2 transposase generated from fossil sequences and shows that the native HSMAR2 is active in human cells, but also in bacteria, with an efficiency similar to other mariner elements. We observe that the sub-cellular localization of HSMAR2 is dependent on the host cell type, and is cytotoxic when overexpressed in HeLa cells. Finally, we also demonstrate that the binding of HSMAR2 to its own ITRs is specific, and that the excision reaction leaves non-canonical footprints both in bacteria and eukaryotic cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Edifici H, Center of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Estel
authors.initials: E
authors.lastname: Gil
authors.forename: Assumpcio
authors.initials: A
authors.lastname: Bosch
authors.forename: David
authors.initials: D
authors.lastname: Lampe
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lizcano
authors.forename: Jose C
authors.initials: JC
authors.lastname: Perales
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: Miguel
authors.initials: M
authors.lastname: Chillon
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001482:Base Composition; D002460:Cell Line; D002470:Cell Survival; D004251:DNA Transposable Elements; D015870:Gene Expression; D005786:Gene Expression Regulation; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D020079:Terminal Repeat Sequences; D019895:Transposases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; C000588815:HSMAR2 protein, human; D019895:Transposases
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