Abstract
Studies in human and mammalian cell cultures have shown that induction of DNA repair mechanisms is required for the formation of stimulation effects of low doses of ionizing radiation, named “hormesis”. Nevertheless, the role of cellular defense mechanisms in the formation of radiation-induced hormesis at the level of whole organism remains poorly studied. The aim of this work was to investigate the role of genes involved in different mechanisms and stages of DNA repair in radioadaptive response and radiation hormesis by lifespan parameters in Drosophila melanogaster. We studied genes that control DNA damage sensing (D-Gadd45, Hus1, mnk), nucleotide excision repair (mei-9, mus210, Mus209), base excision repair (Rrp1), DNA double-stranded break repair by homologous recombination (Brca2, spn-B, okr) and non-homologous end joining (Ku80, WRNexo), and the Mus309 gene that participates in several mechanisms of DNA repair. The obtained results demonstrate that in flies with mutations in studied genes radioadaptive response and radiation hormesis are absent or appear to a lesser extent than in wild-type Canton-S flies. Chronic exposure of γ-radiation in a low dose during pre-imaginal stages of development leads to an increase in expression of the studied DNA repair genes, which is maintained throughout the lifespan of flies. However, the activation of conditional ubiquitous overexpression of DNA repair genes does not induce resistance to an acute exposure to γ-radiation and reinforces its negative impact.
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Acknowledgements
We are grateful to Dr. Schupbach (Princeton University, USA), Dr. Abdu (Ben-Gurion University, Israel), Bloomington (Indiana University, USA) and Kyoto (Kyoto Institute of Technology, Japan) Stock Centers for providing the Drosophila strains. We thank the Genetivision (Houston, USA) for transgenic fly services, to the Drosophila Genomics Resource Center (Indiana University, USA) for cDNA clones.
Funding
The study was carried out within the framework of the state task on themes “Molecular-genetic mechanisms of aging, lifespan, and stress resistance of Drosophila melanogaster”, state registration № AAAA-A18-118011120004-5, “Development of geroprotective and radioprotective agents”, state registration № AAAA-A19-119021590022-2 and complex UrB RAS Programme № 18-7-4-23 “A combination of factors of different nature (low temperature, lack of lighting, restrictive diet, and geroprotector) to maximize the lifespan of Drosophila”, state registration № AAAA-A18-118011120008-3.
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Koval, L., Proshkina, E., Shaposhnikov, M. et al. The role of DNA repair genes in radiation-induced adaptive response in Drosophila melanogaster is differential and conditional. Biogerontology 21, 45–56 (2020). https://doi.org/10.1007/s10522-019-09842-1
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DOI: https://doi.org/10.1007/s10522-019-09842-1