Figure 5.

Ends-out and Ends-in HPV integration mechanisms. In the left panel (ends-out repair), the two linearised microhomologous 3’ ends of the HPV fragment align co-linearly with the target chromosome and perform strand invasion by ends-out replacement of the chromosome sequence with HPV, resulting in a stable deletion of the intervening host sequences. In the right panel (ends-in repair), the two microhomologous 3′ ends align to the target chromosome sequences, only when HPV is in a gapped episomal form. The 3’ ends of the gapped episome can invade and initiate synthesis from the target sequence, creating a chimeric viral chromosome. Repair synthesis occurs by microhomology mediated break-induced replication pathway (MM-BIR). The resulting viral-chromosome chimeric episome can then integrate by homologous recombination into the same copied target sites, resulting in chromosome duplications and amplifications, a transient and recurrent event, predicted to be unstable.