Low dose rate γ-irradiation protects Drosophila melanogaster chromosomes from double strand breaks and telomere fusions by modulating the expression of the esi-RNA biogenesis factor Loquacious

Abstract

It is still continuously debated whether the low-dose/dose-rate (LDDR) of ionizing radiation represents a hazard for humans. Model organisms, such as fruit flies, are considered valuable systems to reveal insights into this issue. We found that, in wild-type Drosophila melanogaster larval neuroblasts, the frequency of Chromosome Breaks (CBs), induced by acute γ-radiation, is significantly reduced when flies are previously exposed to a protracted dose of 0.4 Gy delivered at a dose rate of 2.5 mGy/h. This indicates that this exposure, which is associated with an increased expression of DNA damage response proteins, induces a radioadaptive response (RAR) that protects Drosophila from extensive DNA damage. Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. Deep RNA sequencing revealed that RAR is associated with a modulation of genes involved in RNA processing and the reduction of expression of Loquacious D (Loqs-RD) gene that encodes a well-conserved dsRNA binding protein required for esiRNAs biogenesis. Remarkably, loss of Loqs mimics the LDDR-mediated chromosome protection as it decreases the IR-induced CBs and TF frequency. Thus, our work identifies Loqs as a key factor in mediating the cellular response to LDDR and reveals that the study of the molecular bases underlying RAR is instrumental for unraveling novel and conserved epigenetic routes that have evolved to preserve genome integrity following robust insults to DNA.