L1 expression leads to different types of DNA damage. Schematic structures of an SVA element (labeled SVA), showing the CCCTCT repeat, the Alu-derived (A-like) region, the variable number tandem repeat (VNTR) region, and the long terminal repeat (LTR)-derived region; an Alu element (labeled Alu (SINE)), showing left (purple) and right (pink) halves separated by the A-rich region (A) and the variable length A-tail ((A)n) followed by the 3' region (white), which has a variable length and sequence; and an L1 element (labeled LINE-1), showing open reading frame (ORF)1 (light blue) and ORF2 (dark blue) and the 5' untranslated region, inter-ORF region and 3' untranslated region (white). (a) The typical insertion of these elements into the genome, which can lead to insertional mutagenesis. (b) Dispersed repetitive elements such as Alu elements can undergo non-allelic homologous recombination, which can cause a deletion (shown) or duplication (not shown). The dashed arrow indicates the potential site of DNA damage by an L1 endonuclease that may help initiate these recombination events.(c) Potential outcomes of the repair of the L1-induced double-strand breaks (DSBs). The L1 recognition site is in black; surrounding sequence is in blue; inserted nucleotides are in red. The associated changes are typical of what might be seen with repair of the DSB by non-homologous end joining. It is also possible that the sites are simply re-ligated with no mutation occurring, or alternatively, these sites may cause recombination, as shown in (b).