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Healing the wounds inflicted by Sleeping Beauty transposition by double-strand break repair in mammalian somatic cells

Item Type:Article
Title:Healing the wounds inflicted by Sleeping Beauty transposition by double-strand break repair in mammalian somatic cells
Creators Name:Izsvak, Z. and Stuewe, E.E. and Fiedler, D. and Katzer, A. and Jeggo, P.A. and Ivics, Z.
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.
Keywords:Apoptosis, Base Sequence, Biological Models, Cell Death, CHO Cells, Cricetinae, DNA, DNA Damage, DNA Helicases, DNA Repair, DNA Transposable Elements, DNA-Binding Proteins, Drug Dose-Response Relationship, Enzyme Inhibitors, Genetic Models, Genetic Recombination, Hela Cells, Molecular Sequence Data, Nuclear Antigens, Precipitin Tests, Protein Binding, VDJ Recombinases, Wound Healing, Animals
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press
Volume:13
Number:2
Page Range:279-290
Date:1 January 2004
Official Publication:https://doi.org/10.1016/S1097-2765(03)00524-0
PubMed:View item in PubMed

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