title: ERCC1/XPF limits L1 retrotransposition.
abstract: Retrotransposons are currently active in the human and mouse genomes contributing to novel disease mutations and genomic variation via de novo insertions. However, little is known about the interactions of non-long terminal repeat (non-LTR) retrotransposons with the host DNA repair machinery. Based on the model of retrotransposition for the human and mouse LINE-1 element, one likely intermediate is an extension of cDNA that is heterologous to the genomic target, a flap intermediate. To determine whether a human flap endonuclease could recognize and process this potential intermediate, the genetic requirement for the ERCC1/XPF heterodimer during LINE-1 retrotransposition was characterized. Reduction of XPF in human cells increased retrotransposition whereas complementation of ERCC1-deficiency in hamster cells reduced retrotransposition. These results demonstrate for the first time that DNA repair enzymes act to limit non-LTR retrotransposition and may provide insight into the genetic instability phenotypes of ercc1 and xpf individuals.
authors.affiliation: Tulane Cancer Center and Department of Epidemiology, SL66, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. sgasior@uno.edu <sgasior@uno.edu>
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gasior
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Roy-Engel
authors.forename: Prescott L
authors.initials: PL
authors.lastname: Deininger
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D004720:Endonucleases / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018626:Retroelements
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D018626:Retroelements; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases