The role of DNA repair genes in radiation-induced adaptive response in Drosophila melanogaster is differential and conditional

Oct 19, 2019Biogerontology

DNA Repair Genes Play Different and Conditional Roles in Radiation Adaptation in Fruit Flies

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Abstract

Chronic exposure to low doses of γ-radiation increases the expression of DNA repair genes in Drosophila melanogaster.

Induction of DNA repair mechanisms may be necessary for the effects of low-dose ionizing radiation, known as 'hormesis'.
Mutations in genes responsible for various DNA repair processes result in a diminished or absent radioadaptive response and hormesis in fruit flies.
Low-dose γ-radiation exposure during early development leads to sustained activation of DNA repair gene expression throughout the flies' lifespan.
Conditional overexpression of DNA repair genes does not confer protection against acute γ-radiation exposure and may worsen its effects.

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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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The role of DNA repair genes in radiation-induced adaptive response in Drosophila melanogaster is differential and conditional

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