Identification of an integrase-independent pathway of retrotransposition

Abstract

Retroviruses and long terminal repeat retrotransposons rely on integrase (IN) to insert their complementary DNA (cDNA) into the genome of host cells. Nevertheless, in the absence of IN, retroelements can retain notable levels of insertion activity. We have characterized the IN-independent pathway of Tf1 and found that insertion sites had homology to the primers of reverse transcription, which form single-stranded DNAs at the termini of the cDNA. In the absence of IN activity, a similar bias was observed with HIV-1. Our studies showed that the Tf1 insertions result from single-strand annealing, a noncanonical form of homologous recombination mediated by Rad52. By expanding our analysis of insertions to include repeat sequences, we found most formed tandem elements by inserting at preexisting copies of a related transposable element. Unexpectedly, we found that wild-type Tf1 uses the IN-independent pathway as an alternative mode of insertion.