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 DNAdamaging 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 L1 RP element tagged with enhanced green fluorescent protein. Our results indicate that hydrogen peroxide treatment induces an increase in the retrotransposition of transiently transfected L1 RP 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.

LINE-1 retrotransposition in human neuroblastoma cells is affected by oxidative stress.

GIORGI, GIANFRANCO;DEL RE, BRUNELLA
2011

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 DNAdamaging 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 L1 RP element tagged with enhanced green fluorescent protein. Our results indicate that hydrogen peroxide treatment induces an increase in the retrotransposition of transiently transfected L1 RP 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.
Giorgi G.; Marcantonio P.; Del Re B.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/114325
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