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Abstract
It is still continuously debated whether the low-dose/dose-rate (LDR) 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-irradiation, is considerably 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 LDR 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 reduced 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 LDR-mediated chromosome protection as it decreases the IR-induced CBs and TFs frequency. Thus, our molecular characterization of RAR identifies Loqs as a key factor in the cellular response to LDR and in the epigenetic routes involved in radioresistance.
Chronic low y-radiation exposure to Drosophila cells decreases chromosome breaks induced by high-dose irradiation and telomere dysfunction by reducing the esiRNA biogenesis factor Loquacious D.
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1 Sapienza Università di Roma, Dipartimento di Biologia e Biotecnologie “C. Darwin”, Rome, Italy (GRID:grid.7841.a); Fondazione Cenci Bolognetti/ Istituto Pasteur Italia, Rome, Italy (GRID:grid.452606.3) (ISNI:0000 0004 1764 2528)
2 Fondazione Cenci Bolognetti/ Istituto Pasteur Italia, Rome, Italy (GRID:grid.452606.3) (ISNI:0000 0004 1764 2528); Centro Studi e Ricerche “Enrico Fermi”, Rome, Italy (GRID:grid.449962.4); Università degli Studi della Tuscia, Department of Ecological and Biological Sciences, Viterbo, Italy (GRID:grid.12597.38) (ISNI:0000 0001 2298 9743)
3 Sapienza Università di Roma, Dipartimento di Biologia e Biotecnologie “C. Darwin”, Rome, Italy (GRID:grid.7841.a)
4 Università di Padova, Dipartimento di Biologia, Padua, Italy (GRID:grid.5608.b) (ISNI:0000 0004 1757 3470)
5 INFN-Laboratori Nazionali del Gran Sasso, Assergi, Italy (GRID:grid.466877.c) (ISNI:0000 0001 2201 8832)
6 Istituto Superiore di Sanita‘ ISS, Rome, Italy (GRID:grid.416651.1) (ISNI:0000 0000 9120 6856); INFN-Roma 1, Rome, Italy (GRID:grid.6045.7) (ISNI:0000 0004 1757 5281)
7 INFN-Roma 1, Rome, Italy (GRID:grid.6045.7) (ISNI:0000 0004 1757 5281)