An alternative pathway for Alu retrotransposition suggests a role in DNA double-strand break repair

The Alu family is a highly successful group of non-LTR retrotransposons ubiquitously found in primate genomes. Similar to the L1 retrotransposon family, Alu elements integrate primarily through an endonuclease-dependent mechanism termed target site-primed reverse transcription (TPRT). Recent studies have suggested that, in addition to TPRT, L1 elements occasionally utilize an alternative endonuclease-independent pathway for genomic integration. To determine whether an analogous mechanism exists for Alu elements, we have analyzed three publicly available primate genomes (human, chimpanzee and rhesus macaque) for endonuclease-independent recently integrated or lineage specific Alu insertions. We recovered twenty-three examples of such insertions and show that these insertions are recognizably different from classical TPRT-mediated Alu element integration. We suggest a role for this process in DNA double-strand break repair and present evidence to suggest its association with intra-chromosomal translocations, in-vitro RNA recombination (IVRR), and synthesis-dependent strand annealing (SDSA).