Fig. 5

The TCR pathway prevents the L1 retrotransposon from inserting into the template strand during the transcription of active genes. a If an L1 insertion targets the template strand during the transcription of the gene, it can interfere with the RNAPII complex and stop transcription. CSA and CSB proteins detect the stalled RNAPII and recruit the other proteins of the NER pathway. The elongating L1 cDNA is then cleaved and the original DNA sequence is restored allowing completion of the gene transcription. This process results in the depletion of sense L1 insertions in actively transcribed genes. b If the L1 machinery targets the coding strand during the gene transcription, it does not interfere with the RNAPII complex. The transcription as well as the L1 insertion process can be completed. Thus, a de novo L1 insert ends up in antisense orientation within the active gene