Host DNA repair mechanisms regulate LINE-1 retrotransposition. (A) Shown is a diagram of the cell-based LINE-1 retrotransposition functional assay. A LINE-1 retrotransposition reporter sequence can be expressed in cells using an ectopic expression plasmid. The LINE-1 sequence contains an antisense reporter gene (e.g., eGFP) interrupted by a sense intron in its 3′ UTR, which ensures the reporter gene is only expressed in cells after splicing and retrotransposition of the LINE-1 transcript. Also shown is a list of host DNA repair factors that mediate or inhibit LINE-1 retrotransposition based on functional studies using the cell-based LINE-1 assay. (B) Shown are the sequence structures of genomic outcomes generated by LINE-1 retrotransposition, including full-length insertions, 5′ truncations, 5′ inversions, 3′ transductions, and EN-independent insertions.