Figure 4B(3). Target-primed reverse transcription (TPRT). The L1 retrotransposon is thought to integrate by TPRT. (1) During L1 TPRT, the retrotransposon's endonuclease cleaves one strand of genomic DNA at the target site (grey box) cleaving at the endonuclease consensus site 5’-TT/AAAA-3’: 3’-AA/TTTT-5’, producing a 3’ hydroxyl (OH) at the nick. (2) The retrotransposon RNA base pairs with the exposed genomic DNA strand containing Ts at the nick. (3) The retrotransposon's reverse transcriptase uses the free 3’ OH to prime reverse transcription. Reverse transcription proceeds, producing a cDNA of the retrotransposon RNA. (4) A second break occurs in the other DNA strand of the target site to produce a staggered break. (5) Insertion of the cDNA into the break is completed by an unknown mechanism. (6) Removal of RNA and completion of DNA synthesis produces a complete insertion flanked by target site duplications (TSDs, grey boxes). Roy-Engel, A. M. and Belancio, V. P. 2011. Retrotransposons and Human Disease. eLS. Reproduced as open access material from Wikimedia Commons.