Figure 5.

Model of limitation of damage caused by L1 TPRT via the GGR-NER pathway. The 3′ flap DNA structure is generated by L1 elongating cDNA during TPRT process. The XPC complex recognizes the structure and recruits the other proteins of the NER pathway to the L1 insertion site. ERCC1-XPF endonuclease cleaves the elongating L1 cDNA, inhibiting the insertion of a new L1 element in the genome and leading to the restoration of the original DNA sequence. To a lesser extent, the NER pathway seems to be involved in generating a second nick during the L1 insertion process, in close proximity to the first cleavage generated by the L1 endonuclease. Therefore, in WT cells, the de novo insert is flanked by small (< 100 bp) TSDs, whereas in NER-deficient cells, a more distal unrelated nick may be used to complete the retroelement insertion resulting in large TSDs. cDNA, complementary DNA; GGR, global genome repair; mRNA, messenger RNA; NER, nucleotide excision repair; RNAPII, RNA Polymerase II; TCR, transcription coupled repair; TPRT, target-primed reverse transcription; TSD, target site duplication.