Does the DNA Damage Response Induce Germline Sterility When Transposon Control Is Lost?

Transposable elements (TEs) are genetic parasites that code only for proteins that enable them to jump around in an organism’s genome. TE proliferation can be extremely damaging to the host, especially if TEs land in coding regions of the genome. A class of small RNAs called piRNAs form RNA-protein complexes that serve as protection factors to target and destroy transposable elements through sequence homology. piRNAs are maternally inherited, so when a male fly that contains a particular transposable element is crossed with a female fly that does not, the resulting progeny lack the protection factor and the TE is able to propagate throughout the germline. This leads to hybrid dysgenesis, a syndrome associated with sterility in the F1 generation. The proposed pathway leading to sterility starts with TE mobilization, which causes double-stranded breaks and germline DNA damage. Double-stranded breaks in the DNA activate the ATM/ATR checkpoint pathway, which eventually causes the cell cycle to arrest and the cell to undergo apoptosis. A previous study looked at flies defective for the ability to control TEs through the piRNA pathway. They found that maternal caffeine treatments can rescue a dorsal appendage phenotype, induced by TE mediated DNA damage, by inhibiting the DNA damage response. We hypothesized that maternal caffeine treatments in D. virilis would have the same effect on testes of male progeny from dysgenic crosses. After analyzing the results of this experiment, we find that the sterility phenotype may be independent of the DNA damage response.