title: Healing the wounds inflicted by sleeping beauty transposition by double-strand break repair in mammalian somatic cells.
abstract: The Sleeping Beauty (SB) element is a useful tool to probe transposon-host interactions in vertebrates. We investigated requirements of DNA repair factors for SB transposition in mammalian cells. Factors of nonhomologous end joining (NHEJ), including Ku, DNA-PKcs, and Xrcc4 as well as Xrcc3/Rad51C, a complex that functions during homologous recombination, are required for efficient transposition. NHEJ plays a dominant role in repair of transposon excision sites in somatic cells. Artemis is dispensable for transposition, consistent with the lack of a hairpin structure at excision sites. Ku physically interacts with the SB transposase. DNA-PKcs is a limiting factor for transposition and, in addition to repair, has a function in transposition that is independent from its kinase activity. ATM is involved in excision site repair and affects transposition rates. The overlapping but distinct roles of repair factors in transposition and in V(D)J recombination might influence the outcomes of these mechanistically similar processes.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, D-13092 Berlin, Germany.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Izsvák
authors.forename: Eva E
authors.initials: EE
authors.lastname: Stüwe
authors.forename: Dora
authors.initials: D
authors.lastname: Fiedler
authors.forename: Andrea
authors.initials: A
authors.lastname: Katzer
authors.forename: Penny A
authors.initials: PA
authors.lastname: Jeggo
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ivics
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D016466:CHO Cells; D016923:Cell Death; D006224:Cricetinae; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004251:DNA Transposable Elements / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D011995:Recombination, Genetic; D045567:VDJ Recombinases / Q000378:metabolism; D014945:Wound Healing
chemical_list: D034961:Antigens, Nuclear; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C110901:X-ray repair cross complementing protein 3; C101467:XRCC4 protein, human; D004247:DNA; D045567:VDJ Recombinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen