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

  • Liubov Koval
  • Ekaterina Proshkina
  • Mikhail Shaposhnikov
  • Alexey MoskalevEmail author
Research Article

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.

Keywords

Drosophila melanogaster Lifespan DNA repair genes Radioadaptive response Radiation hormesis Ionizing radiation 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplementary material

10522_2019_9842_MOESM1_ESM.pdf (336 kb)
Supplementary material 1 (PDF 336 kb)

References

  1. Abdu U, Klovstad M, Butin-Israeli V, Bakhrat A, Schupbach T (2007) An essential role for Drosophila hus1 in somatic and meiotic DNA damage responses. J Cell Sci 120:1042–1049.  https://doi.org/10.1242/jcs.03414 CrossRefPubMedGoogle Scholar
  2. Ashburner M (1989) Drosophila: A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NYGoogle Scholar
  3. Bao L, Ma J, Chen G, Hou J, Hei TK, Yu KN, Han W (2016) Role of heme oxygenase-1 in low dose radioadaptive response. Redox Biol 8:333–340.  https://doi.org/10.1016/j.redox.2016.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Booth LN, Brunet A (2016) The aging epigenome. Mol Cell 62:728–744.  https://doi.org/10.1016/j.molcel.2016.05.013 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Boubriak I, Mason PA, Clancy DJ, Dockray J, Saunders RD, Cox LS (2009) DmWRNexo is a 3′-5′ exonuclease: phenotypic and biochemical characterization of mutants of the Drosophila orthologue of human WRN exonuclease. Biogerontology 10:267–277.  https://doi.org/10.1007/s10522-008-9181-3 CrossRefPubMedGoogle Scholar
  6. Breslow N, Zandstra R (1970) A note on the relationship between bone marrow lymphocytosis and remission duration in acute leukemia. Blood 36:246–249CrossRefGoogle Scholar
  7. Brough R, Wei D, Leulier S, Lord CJ, Rong YS, Ashworth A (2008) Functional analysis of Drosophila melanogaster BRCA2 in DNA repair. DNA Repair 7:10–19.  https://doi.org/10.1016/j.dnarep.2007.07.013 CrossRefPubMedGoogle Scholar
  8. Caplin N, Willey N (2018) Ionizing radiation, higher plants, and radioprotection: from acute high doses to chronic low doses. Front Plant Sci 9:847.  https://doi.org/10.3389/fpls.2018.00847 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cortese F et al (2018) Vive la radioresistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization. Oncotarget 9:14692–14722.  https://doi.org/10.18632/oncotarget.24461 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Costantino S, Camici GG, Mohammed SA, Volpe M, Luscher TF, Paneni F (2018) Epigenetics and cardiovascular regenerative medicine in the elderly. Int J Cardiol 250:207–214.  https://doi.org/10.1016/j.ijcard.2017.09.188 CrossRefPubMedGoogle Scholar
  11. Dehghani L et al (2013) Evaluation of neural gene expression in serum treated embryonic stem cells in Alzheimer’s patients. J Res Med Sci 18:S20–S23PubMedPubMedCentralGoogle Scholar
  12. Devic C, Ferlazzo ML, Foray N (2018) Influence of individual radiosensitivity on the adaptive response phenomenon: toward a mechanistic explanation based on the nucleo-shuttling of ATM protein. Dose-Response 16:1559325818789836.  https://doi.org/10.1177/1559325818789836 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Doroszuk A, Jonker MJ, Pul N, Breit TM, Zwaan BJ (2012) Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension. BMC Genom 13:167.  https://doi.org/10.1186/1471-2164-13-167 CrossRefGoogle Scholar
  14. Fleming TR, O’Fallon JR, O’Brien PC (1980) Modified Kolmogorov-Smirnov test procedures with application to arbitrarily right-censored data. Biometrics 36:607–625CrossRefGoogle Scholar
  15. Gavrilov LA, Gavrilova NS (1991) The biology of life span: a quantitative approach. Harwood Academic Publisher, New YorkGoogle Scholar
  16. Ghabrial A, Ray RP, Schupbach T (1998) okra and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev 12:2711–2723.  https://doi.org/10.1101/gad.12.17.2711 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Gueguen Y, Bontemps A, Ebrahimian TG (2018) Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms. Cell Mol Life Sci.  https://doi.org/10.1007/s00018-018-2987-5 CrossRefPubMedGoogle Scholar
  18. Halmosi R, Berente Z, Osz E, Toth K, Literati-Nagy P, Sumegi B (2001) Effect of poly(ADP-ribose) polymerase inhibitors on the ischemia-reperfusion-induced oxidative cell damage and mitochondrial metabolism in Langendorff heart perfusion system. Mol Pharmacol 59:1497–1505.  https://doi.org/10.1124/mol.59.6.1497 CrossRefPubMedGoogle Scholar
  19. Henderson DS, Wiegand UK, Norman DG, Glover DM (2000) Mutual correction of faulty PCNA subunits in temperature-sensitive lethal mus209 mutants of Drosophila melanogaster. Genetics 154:1721–1733PubMedPubMedCentralGoogle Scholar
  20. Henning KA, Peterson C, Legerski R, Friedberg EC (1994) Cloning the Drosophila homolog of the xeroderma pigmentosum complementation group C gene reveals homology between the predicted human and Drosophila polypeptides and that encoded by the yeast RAD4 gene. Nucleic Acids Res 22:257–261.  https://doi.org/10.1093/nar/22.3.257 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kadir R, Bakhrat A, Tokarsky R, Abdu U (2012) Localization of the Drosophila Rad9 protein to the nuclear membrane is regulated by the C-terminal region and is affected in the meiotic checkpoint. PLoS ONE 7:e38010.  https://doi.org/10.1371/journal.pone.0038010 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kim SN et al (2005) Age-dependent changes of gene expression in the Drosophila head. Neurobiol Aging 26:1083–1091.  https://doi.org/10.1016/j.neurobiolaging.2004.06.017 CrossRefPubMedGoogle Scholar
  23. Kooistra R, Pastink A, Zonneveld JB, Lohman PH, Eeken JC (1999) The Drosophila melanogaster DmRAD54 gene plays a crucial role in double-strand break repair after P-element excision and acts synergistically with Ku70 in the repair of X-ray damage. Mol Cell Biol 19:6269–6275.  https://doi.org/10.1128/mcb.19.9.6269 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Kusano K, Johnson-Schlitz DM, Engels WR (2001) Sterility of Drosophila with mutations in the Bloom syndrome gene—complementation by Ku70. Science 291:2600–2602.  https://doi.org/10.1126/science.291.5513.2600 CrossRefPubMedGoogle Scholar
  25. Le Bourg E (2009) Hormesis, aging and longevity. Biochem Biophys Acta 1790:1030–1039.  https://doi.org/10.1016/j.bbagen.2009.01.004 CrossRefPubMedGoogle Scholar
  26. Lee JS, Ward WO, Wolf DC, Allen JW, Mills C, DeVito MJ, Corton JC (2008) Coordinated changes in xenobiotic metabolizing enzyme gene expression in aging male rats. Toxicol Sci 106:263–283.  https://doi.org/10.1093/toxsci/kfn144 CrossRefPubMedGoogle Scholar
  27. Ma DK, Guo JU, Ming GL, Song H (2009) DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation. Cell Cycle 8:1526–1531.  https://doi.org/10.4161/cc.8.10.8500 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Mao Z, Tian X, Van Meter M, Ke Z, Gorbunova V, Seluanov A (2012) Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proc Natl Acad Sci USA 109:11800–11805.  https://doi.org/10.1073/pnas.1200583109 CrossRefPubMedGoogle Scholar
  29. Mattson MP, Calabrese EJ (2010) Hormesis: a revolution in biology. Springer, New York, Toxicology and Medicine.  https://doi.org/10.1007/978-1-60761-495-1 CrossRefGoogle Scholar
  30. Moskalev A (2007) Radiation-induced life span alteration of Drosophila lines with genotype differences. Biogerontology 8:499–504.  https://doi.org/10.1007/s10522-007-9090-x CrossRefPubMedGoogle Scholar
  31. Moskalev AA, Pliusnina EN, Zainullin VG (2007) The influence of low doze gamma-irradiation on life span of Drosophila mutants with defects of DNA damage sensation and repair. Radiatsionnaia Biol, Radioecol/Ross Akad Nauk 47:571–573Google Scholar
  32. Moskalev A, Shaposhnikov M, Turysheva E (2009) Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps. Biogerontology 10:3–11.  https://doi.org/10.1007/s10522-008-9147-5 CrossRefPubMedGoogle Scholar
  33. Moskalev AA, Plyusnina EN, Shaposhnikov MV (2011) Radiation hormesis and radioadaptive response in Drosophila melanogaster flies with different genetic backgrounds: the role of cellular stress-resistance mechanisms. Biogerontology 12:253–263.  https://doi.org/10.1007/s10522-011-9320-0 CrossRefPubMedGoogle Scholar
  34. Moskalev A, Plyusnina E, Shaposhnikov M, Shilova L, Kazachenok A, Zhavoronkov A (2012) The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance. Cell Cycle 11:4222–4241.  https://doi.org/10.4161/cc.22545 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Moskalev A, Shaposhnikov M, Plyusnina E, Plyusnin S, Shostal O, Aliper A, Zhavoronkov A (2014a) Exhaustive data mining comparison of the effects of low doses of ionizing radiation, formaldehyde and dioxins. BMC Genom 15(Suppl 12):S5.  https://doi.org/10.1186/1471-2164-15-S12-S5 CrossRefGoogle Scholar
  36. Moskalev A et al (2014b) Mining gene expression data for pollutants (dioxin, toluene, formaldehyde) and low dose of gamma-irradiation. PLoS ONE 9:e86051.  https://doi.org/10.1371/journal.pone.0086051 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Moskalev A et al (2015) A comparison of the transcriptome of Drosophila melanogaster in response to entomopathogenic fungus, ionizing radiation, starvation and cold shock. BMC Genom 16(Suppl 13):S8.  https://doi.org/10.1186/1471-2164-16-S13-S8 CrossRefGoogle Scholar
  38. Osterwalder T, Yoon KS, White BH, Keshishian H (2001) A conditional tissue-specific transgene expression system using inducible GAL4. Proc Natl Acad Sci USA 98:12596–12601.  https://doi.org/10.1073/pnas.221303298 CrossRefPubMedGoogle Scholar
  39. Paszkowska-Szczur K et al (2013) Xeroderma pigmentosum genes and melanoma risk. Int J Cancer 133:1094–1100.  https://doi.org/10.1002/ijc.28123 CrossRefPubMedGoogle Scholar
  40. Paunesku T, Woloschak GE (2017) Future directions of intraoperative radiation therapy: a brief review. Front Oncol 7:300.  https://doi.org/10.3389/fonc.2017.00300 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Plyusnina EN, Shaposhnikov MV, Moskalev AA (2011) Increase of Drosophila melanogaster lifespan due to D-GADD45 overexpression in the nervous system. Biogerontology 12:211–226.  https://doi.org/10.1007/s10522-010-9311-6 CrossRefPubMedGoogle Scholar
  42. Poljsak B, Milisav I (2016) NAD+ as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and health span. Rejuvenation Res.  https://doi.org/10.1089/rej.2015.1767 CrossRefPubMedGoogle Scholar
  43. Rapin I (2013) Disorders of nucleotide excision repair. Handb Clin Neurol 113:1637–1650.  https://doi.org/10.1016/B978-0-444-59565-2.00032-0 CrossRefPubMedGoogle Scholar
  44. Rattan SI (2010) Targeting the age-related occurrence, removal, and accumulation of molecular damage by hormesis. Ann N Y Acad Sci 1197:28–32.  https://doi.org/10.1111/j.1749-6632.2010.05193.x CrossRefPubMedGoogle Scholar
  45. Ruike T et al (2006) Characterization of a second proliferating cell nuclear antigen (PCNA2) from Drosophila melanogaster. FEBS J 273:5062–5073.  https://doi.org/10.1111/j.1742-4658.2006.05504.x CrossRefPubMedGoogle Scholar
  46. Sander M, Huang SM (1995) Characterization of the nuclease activity of Drosophila Rrp1 on phosphoglycolate- and phosphate-modified DNA 3′-termini. Biochemistry 34:1267–1274CrossRefGoogle Scholar
  47. Saunders LR, Verdin E (2009) Cell biology. Stress Response Aging Sci 323:1021–1022.  https://doi.org/10.1126/science.1170007 CrossRefGoogle Scholar
  48. Sayed-Ahmed MM, Al-Shabanah OA, Hafez MM, Aleisa AM, Al-Rejaie SS (2010) Inhibition of gene expression of heart fatty acid binding protein and organic cation/carnitine transporter in doxorubicin cardiomyopathic rat model. Eur J Pharmacol 640:143–149.  https://doi.org/10.1016/j.ejphar.2010.05.002 CrossRefPubMedGoogle Scholar
  49. Schriner SE et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911.  https://doi.org/10.1126/science.1106653 CrossRefGoogle Scholar
  50. Sekelsky JJ, Brodsky MH, Burtis KC (2000) DNA repair in Drosophila: insights from the Drosophila genome sequence. J Cell Biol 150:F31–F36CrossRefGoogle Scholar
  51. Shrestha S, Vanasse A, Cooper LN, Antosh MP (2017) Gene expression as a dosimeter in irradiated Drosophila melanogaster. J Comput Biol 24:1265–1274.  https://doi.org/10.1089/cmb.2017.0170 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Sibille E (2013) Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders. Dialogues Clin Neurosci 15:53–65PubMedPubMedCentralGoogle Scholar
  53. Staeva-Vieira E, Yoo S, Lehmann R (2003) An essential role of DmRad51/SpnA in DNA repair and meiotic checkpoint control. EMBO J 22:5863–5874.  https://doi.org/10.1093/emboj/cdg564 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Sthijns MM, Weseler AR, Bast A, Haenen GR (2016) Time in redox adaptation processes: from evolution to hormesis. Int J Mol Sci.  https://doi.org/10.3390/ijms17101649 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Taccioli GE et al (1994) Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science 265:1442–1445.  https://doi.org/10.1126/science.8073286 CrossRefPubMedGoogle Scholar
  56. Takeuchi R et al (2006) Drosophila DNA polymerase ζ interacts with recombination repair protein 1, the Drosophila homologue of human abasic endonuclease 1. J Biol Chem 281:11577–11585.  https://doi.org/10.1074/jbc.M512959200 CrossRefPubMedGoogle Scholar
  57. Tugay TI, Zheltonozhskaya MV, Sadovnikov LV, Tugay AV, Farfan EB (2011) Effects of ionizing radiation on the antioxidant system of microscopic fungi with radioadaptive properties found in the Chernobyl exclusion zone. Health Phys 101:375–382.  https://doi.org/10.1097/HP.0b013e3181f56bf8 CrossRefPubMedGoogle Scholar
  58. Valerie K, Yacoub A, Hagan MP, Curiel DT, Fisher PB, Grant S, Dent P (2007) Radiation-induced cell signaling: inside-out and outside-in. Mol Cancer Ther 6:789–801.  https://doi.org/10.1158/1535-7163.MCT-06-0596 CrossRefPubMedGoogle Scholar
  59. Viswanathan M, Kim SK, Berdichevsky A, Guarente L (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 9:605–615.  https://doi.org/10.1016/j.devcel.2005.09.017 CrossRefPubMedGoogle Scholar
  60. Wang C, Li Q, Redden DT, Weindruch R, Allison DB (2004) Statistical methods for testing effects on “maximum lifespan”. Mech Ageing Dev 125:629–632.  https://doi.org/10.1016/j.mad.2004.07.003 CrossRefPubMedGoogle Scholar
  61. Weinert BT, Rio DC (2007) DNA strand displacement, strand annealing and strand swapping by the Drosophila Bloom’s syndrome helicase. Nucleic Acids Res 35:1367–1376.  https://doi.org/10.1093/nar/gkl831 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Whigham BT, Allingham RR (2011) Review: the role of LOXL1 in exfoliation syndrome/glaucoma. Saudi J Ophthalmol 25:347–352.  https://doi.org/10.1016/j.sjopt.2011.07.001 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Yildiz O, Kearney H, Kramer BC, Sekelsky JJ (2004) Mutational analysis of the Drosophila DNA repair and recombination gene mei-9. Genetics 167:263–273CrossRefGoogle Scholar
  64. Zhikrevetskaya S et al (2015) Effect of low doses (5-40 cGy) of gamma-irradiation on lifespan and stress-related genes expression profile in Drosophila melanogaster. PLoS ONE 10:e0133840.  https://doi.org/10.1371/journal.pone.0133840 CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory of Geroprotective and Radioprotective TechnologiesInstitute of Biology, Komi Science Center, Ural Branch, Russian Academy of SciencesSyktyvkarRussian Federation
  2. 2.Pitirim Sorokin Syktyvkar State UniversitySyktyvkarRussian Federation
  3. 3.Laboratory of Post-Genomic ResearchEngelhardt Institute of Molecular Biology, Russian Academy of SciencesMoscowRussian Federation
  4. 4.Moscow Institute of Physics and TechnologyDolgoprudnyRussian Federation

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