Abstract
Long interspersed element-1s (LINE-1 or L1s) are abundant retrotransposons that occur in mammalian genomes and that can cause insertional mutagenesis and genomic instability. L1 activity is generally repressed in most cells and tissues but has been found in some embryonic cells and, in particular, in neural progenitors. Moreover, L1 retrotransposition can be induced by several DNA-damaging agents. We have carried out experiments to verify whether L1 retrotransposition is affected by oxidative DNA damage, which plays a role in a range of human diseases, including cancer and inflammatory and neurodegenerative disease. To this purpose, BE(2)C neuroblastoma cells, which are thought to represent embryonic precursors of sympathetic neurons, have been treated with hydrogen peroxide and subjected to an in vitro retrotransposition assay involving an episomal L1RP element tagged with enhanced green fluorescent protein. Our results indicate that hydrogen peroxide treatment induces an increase in the retrotransposition of transiently transfected L1RP and an increase in the expression of endogenous L1 transcripts. An increase of γ-H2AX foci and changes in the mRNA levels of MRE11, RAD50, NBN and ERCC1 (all involved in DNA repair) have also been found. Thus, oxidative stress can cause L1 dysregulation.
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This work was supported by the “Electromagnetic field effects on neuronal cells” PRIN-2007 program from the Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca).
The authors declare no conflicts of interest and they alone are responsible for the content and writing of this paper.
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Giorgi, G., Marcantonio, P. & Del Re, B. LINE-1 retrotransposition in human neuroblastoma cells is affected by oxidative stress. Cell Tissue Res 346, 383–391 (2011). https://doi.org/10.1007/s00441-011-1289-0
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DOI: https://doi.org/10.1007/s00441-011-1289-0