DNA repair strategy sets transposon mobilization rates in Caenorhabditis elegans

Transposons are parasitic nucleic acids that threaten genome integrity in all cells. In the metazoan model organism Caenorhabditis elegans, DNA transposons are active in the soma where they are reported to exhibit mobilization rates {cong}1000 fold higher than in germ cells. How and why DNA transposons might be so highly active in the C. elegans soma is a mystery. To better understand this question, we constructed reporter genes that label cells in which Tc1 has mobilized with fluorescent protein. The reporters recapitulate the known properties of DNA transposons in C. elegans and allow transposon activity to be monitored in intact, living animals. Using these reporters, we identify cytoplasmic and nuclear factors that limit transposition in the germline. Interestingly, none of these factors limit transposition in the soma. Rather, we identify a gene (nhj-1/scb-1), which we show is required for 99.9% of Tc1 mobilization events in somatic tissues, but does not influence mobilization in the germline. nhj-1/scb-1 encodes a nematode-specific component of the non-homologous end joining (NHEJ) DNA repair machinery. Mutations in the other components of the NHEJ machinery (cku-70, cku-80, and lig-4) also suppress Tc1 mobilization in the C. elegans soma by {cong}1000 fold. The data show that the use of NHEJ to repair transposon-induced DNA breaks in the soma dramatically increases the rate of transposon mobilization in this tissue. And because C. elegans germ cells use homology-based repair, and not NHEJ, to fix transposon-induced breaks, we propose that the 1000-fold difference in transposon mobility reported for the C. elegans soma and germline can, in large part, be explained by tissue-specific differences in DNA repair strategy. Author SummaryTransposons are common parasitic genetic elements that threaten all genomes. For example, half of the human genome is made up of transposons. Transposon mobilization can disrupt gene function, causing disease, so transposon activity needs to be tightly regulated to prevent harm to the host. Transposons are typically less active in the soma than in the germline, because somatic transposition benefits neither host or transposon. Surprisingly, in the nematode model organism Caenorhabditis elegans, transposons are reported to be 1000-fold more active in the soma than the germline. Here, we develop a system to investigate transposon regulation in an intact live animal, and show that, in large part, tissue-specific differences in transposon activity in C. elegans is due to the use of different DNA repair pathways by these tissues, highlighting the importance of DNA repair strategy in determining outcomes of transposon excision events. Given that DNA repair factors have been linked to transposon regulation in other eukaryotes, we propose that DNA repair choice likely contributes to transposon mobilization in all eukaryotes.