Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Noncanonical Functions of the Human Ribosomal Repeat

  • 3 Accesses

Abstract

Ribosomal genes encode ribosomal RNA (rRNA), which is an integral part of ribosomes. The main function of ribosomal genes in the cell is the synthesis of rRNA. However, ribosomal genes can also perform other functions in the body. It was found that DNA of ribosomal genes (rDNA) is an active biomolecule, which can be attributed to the family of DAMPs (danger-associated molecular patterns). Three unusual characteristics of rDNA confer to it the properties of a DAMP molecule: (1) high content of unmethylated CpG motifs—ligands of DNA sensing TLR9; (2) low oxidation potential; and (3) resistance to fragmentation under the accumulation of single-strand breaks in rDNA chains. Owing to these properties, rDNA fragments are accumulated as a part of circulating extracellular DNA and stimulate the TLR9–MyD88–NF-kB signaling pathway in various cells of the body. Oxidized rDNA permeates into the cells, where it can stimulate other DNA sensors (AIM2, RIG1, STING). Extracellular oxidized rDNA reaches the structures of the nucleolus and affects the level of rRNA in the cell. The body defends itself against the excess of extracellular rDNA by producing antibodies to rDNA, which form much stronger complexes with rDNA than common antibodies to double-stranded DNA. It is reasonable to further study extracellular rDNA as a potential target in the treatment of autoimmune, oncological, and cardiovascular diseases.

This is a preview of subscription content, log in to check access.

Fig. 1.
Fig. 2.

REFERENCES

  1. 1

    Khatter, H., Myasnikov, A.G., Natchiar, S.K., and Klaholz, B.P., Structure of the human 80S ribosome, Nature, 2015, vol. 520, no. 7549, no. 30, pp. 640–645. https://doi.org/10.1038/nature14427

  2. 2

    McStay, B. and Grummt, I., The epigenetics of rRNA genes: from molecular to chromosome biology, Annu. Rev. Cell Dev. Biol., 2008, vol. 24, pp. 131–157. https://doi.org/10.1146/annurev.cellbio.24.110707.175259

  3. 3

    Hamperl, S., Wittner, M., Babl, V., et al., Chromatin states at ribosomal DNA loci, Biochim. Biophys. Acta, 2013, vol. 1829, nos. 3–4, pp. 405–417. https://doi.org/10.1016/j.bbagrm.2012.12.007

  4. 4

    Lyapunova, N.A., Veiko, N., and Porokhovnik, L., Human rDNA genes: identification of four fractions, their functions and nucleolar location, Proteins of the Nucleolus: Regulation, Translocation, and Biomedical Functions, O’Day, D.H. and Catalano, A., Eds., Dordrecht: Springer-Verlag, 2013, pp. 95–118.

  5. 5

    Conconi, A., Widmer, R.M., Koller, T., et al., Two different chromatin structures coexist in ribosomal RNA genes throughout the cell cycle, Cell, 1989, vol. 57, no. 5, pp. 753–761.

  6. 6

    French, S.L., Osheim, Y.N., Cioci, F., et al., In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes, Mol. Cell. Biol., 2003, vol. 23, no. 5, pp. 1558–1568.

  7. 7

    Lyapunova, N.A. and Veiko, N.N., Ribosomal genes in the human genome: identification of four fractions, their organization in the nucleolus and metaphase chromosomes, Russ. J. Genet., 2010, vol. 46, no. 9, pp. 1070–1073. https://doi.org/10.1134/S1022795410090140

  8. 8

    Malinovskaya, E.M., Ershova, E.S., Golimbet, V.E., et al., Copy number of human ribosomal genes with aging: unchanged mean, but narrowed range and decreased variance in elderly group, Front. Genet., 2018, vol. 9, no. 7, p. 306. https://doi.org/10.3389/fgene.2018.00306

  9. 9

    Paredes, S., Branco, A.T., Hartl, D.L., et al., Ribosomal DNA deletions modulate genome-wide gene expression: “rDNA-sensitive” genes and natural variation, PLoS Genet., 2011, vol. 7, no. 4. e1001376. https://doi.org/10.1371/journal.pgen.1001376

  10. 10

    Kobayashi, T., Ribosomal RNA gene repeats, their stability and cellular senescence, Proc. Jpn. Acad.,Ser. B, 2014, vol. 90, no. 4, pp. 119–129.

  11. 11

    Bianchi, M.E., DAMPs, PAMPs and alarmins: all we need to know about danger, J. Leukoc Biol., 2007, vol. 81, no. 1, pp. 1–5. https://doi.org/10.1189/jlb.0306164

  12. 12

    Janeway, C.A., Jr., The immune system evolved to discriminate infectious nonself from noninfectious self, Immunol. Today, 1992, vol. 13, no. 1, pp. 11–16. https://doi.org/10.1016/0167-5699(92)90198-G

  13. 13

    Matzinger, P., The danger model: a renewed sense of self, Science, 2002, vol. 296, no. 12, pp. 301–305. https://doi.org/10.1126/science.1071059

  14. 14

    Matzinger, P., Tolerance, danger, and the extended family, Annu. Rev. Immunol., 1994, vol. 12, pp. 991–1045. https://doi.org/10.1146/annurev.iy.12.040194.005015

  15. 15

    Chan, J.K., Roth, J., Oppenheim, J.J., et al., Alarmins: awaiting a clinical response, J. Clin. Invest., 2012, vol. 122, pp. 2711–2719. https://doi.org/10.1172/JCI62423

  16. 16

    Pisetsky, D.S., The origin and properties of extracellular DNA: from PAMP to DAMP, Clin. Immunol., 2012, vol. 144, no. 1, pp. 32–40. https://doi.org/10.1016/j.clim.2012.04.006

  17. 17

    Kato, J. and Svensson, C.I., Role of extracellular damage-associated molecular pattern molecules (DAMPs) as mediators of persistent pain, Prog. Mol. Biol. Transl. Sci., 2015, vol. 131, pp. 251–279. https://doi.org/10.1016/bs.pmbts.2014.11.014

  18. 18

    Magna, M. and Pisetsky, D.S., The alarmin properties of DNA and DNA-associated nuclear proteins, Clin. Ther., 2016, vol. 38, no. 5, pp. 1029–1041. https://doi.org/10.1016/j.clinthera.2016.02.029

  19. 19

    Pös, O., Biró, O., Szemes, T., and Nagy, B., Circulating cell-free nucleic acids: characteristics and applications, Eur. J. Hum. Genet., 2018, vol. 26, no. 7, pp. 937–945. https://doi.org/10.1038/s41431-018-0132-4

  20. 20

    Aucamp, J., Bronkhorst, A.J., Badenhorst, C.P.S., and Pretorius, P.J., The diverse origins of circulating cell-free DNA in the human body: a critical re-evaluation of the literature, Biol. Rev. Camb. Philos Soc., 2018, vol. 93, no. 3, pp. 1649–1683. https://doi.org/10.1111/brv.12413

  21. 21

    Thierry, A.R., Messaoudi, S., Gahan, P.B., et al., Origins, structures, and functions of circulating DNA in oncology, Cancer Metastasis Rev., 2016, vol. 35, no. 3, pp. 347–376. https://doi.org/10.1007/s10555-016-9629-x

  22. 22

    Puszyk, W.M., Crea, F., and Old, R.W., Unequal representation of different unique genomic DNA sequences in the cell-free plasma DNA of individual donors, Clin. Biochem., 2009, vol. 42, nos. 7–8, pp. 736–738. https://doi.org/10.1016/j.clinbiochem.2008.11.006

  23. 23

    Veiko, N.N., Shubaeva, N.O., Ivanova, S.M., et al., Blood serum DNA in patients with rheumatoid arthritis is considerably enriched with fragments of ribosomal repeats containing immunostimulatory CpG-motifs, Bull. Exp. Biol. Med., 2006, vol. 142, pp. 313–316.

  24. 24

    Korzeneva, I.B., Kostuyk, S.V., and Ershova, E.S., et al., Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma-neutron and tritium beta-radiation, Mutat. Res., 2016, vol. 791–792, pp. 49–60. https://doi.org/10.1016/j.mrfmmm.2016.09.001

  25. 25

    Veiko, N.N., Bulycheva, N.A., Veiko, R.V., et al., Ribosomal repeat in the cell free DNA as a marker for cell death, Biochem.(Moscow), Suppl., Ser. B,Biomed. Chem., 2008, vol. 2, pp. 198–207.

  26. 26

    Aswani, A., Manson, J., Itagaki, K., et al., Scavenging circulating mitochondrial DNA as a potential therapeutic option for multiple organ dysfunction in trauma hemorrhage, Front. Immunol., 2018, vol. 8, no. 9, p. 891. https://doi.org/10.3389/fimmu.2018.00891

  27. 27

    Ershova, E.S., Jestkova, E.M., Chestkov, I.V., et al., Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients, J. Psychiatr. Res., 2017, vol. 87, pp. 15–22. https://doi.org/10.1016/j.jpsychires.2016.12.006

  28. 28

    Feng, H., Jin, P., and Wu, H., Disease prediction by cell-free DNA methylation, Brief Bioinf., 2018. https://doi.org/10.1093/bib/bby029

  29. 29

    Jung, M., Kristiansen, G., and Dietrich, D., DNA methylation analysis of free-circulating DNA in body fluids, Methods Mol. Biol., 2018, vol. 1708, pp. 621–641. https://doi.org/10.1007/978-1-4939-7481-8_32

  30. 30

    Dietrich, D., DNA methylation analysis from body fluids., Methods Mol. Biol., 2018, vol. 1655, pp. 239–249. https://doi.org/10.1007/978-1-4939-7234-0_18

  31. 31

    Sano, H. and Morimoto, C., DNA isolated from DNA/anti-DNA antibody immune complexes in systemic lupus erythematosus is rich in guanine—cytosine content, J. Immunol., 1982, vol. 128, pp. 1341–1345.

  32. 32

    Lander, E.S., Linton, L.M., Birren, B., et al., Initial sequencing and analysis of the human genome, Nature, 2001, vol. 409, no. 6822, pp. 860–921.

  33. 33

    Zhang, J.Z., Liu, Z., Liu, J., et al., Mitochondrial DNA induces inflammation and increases TLR9/NF-κB expression in lung tissue, Int. J. Mol. Med., 2014, vol. 33, no. 4, pp. 817–824. https://doi.org/10.3892/ijmm.2014.1650

  34. 34

    Honda, K. and Taniguchi, T., IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors, Nat. Rev. Immunol., 2006, vol. 6, no. 9, pp. 644–658. https://doi.org/10.1038/nri1900

  35. 35

    Bauer, S., Kirschning, C.J., Häcker, H., Redecke, V., et al., Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition, Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, no. 16, pp. 9237–9242. https://doi.org/10.1073/pnas.161293498

  36. 36

    Wu, B., Ni, H., Li, J., et al., The impact of circulating mitochondrial DNA on cardiomyocyte apoptosis and myocardial injury after TLR4 activation in experimental autoimmune myocarditis, Cell Physiol. Biochem., 2017, vol. 42, no. 2, pp. 713–728. https://doi.org/10.1159/000477889

  37. 37

    Liu, Y., Yan, W., Tohme, S., et al., Hypoxia induced HMGB1 and mitochondrial DNA interactions mediate tumor growth in hepatocellular carcinoma through Toll-like receptor 9, J. Hepatol., 2015, vol. 63, no. 1, pp. 114–121. https://doi.org/10.1016/j.jhep.2015.02.009

  38. 38

    Zhang, Q., Raoof, M., Chen, Y., et al., Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature, 2010, vol. 464, no. 7285, pp. 104–107. https://doi.org/10.1038/nature08780

  39. 39

    Nakahira, K., Hisata, S., and Choi, A.M., The roles of mitochondrial damage-associated molecular patterns in diseases, Antioxid. Redox. Signal., 2015, vol. 23, no. 17, pp. 1329–1350. https://doi.org/10.1089/ars.2015.6407

  40. 40

    Walko, T.D., Bola, R.A., and Hong, J.D., Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury, Shock, vol. 41, no. 6, pp. 499–503. https://doi.org/10.1097/SHK.0000000000000160

  41. 41

    Wenceslau, C.F., McCarthy, C.G., Szasz, T., et al., Working group on DAMPs in cardiovascular disease: mitochondrial damage-associated molecular patterns and vascular function, Eur. Heart J., 2014, vol. 35, no. 18, pp. 1172–1177. https://doi.org/10.1093/eurheartj/ehu047

  42. 42

    Handa, P., Vemulakonda, A., Kowdley, K.V., et al., Mitochondrial DNA from hepatocytes as a ligand for TLR9: drivers of nonalcoholic steatohepatitis?, World J. Gastroenterol., 2016, vol. 22, no. 31, pp. 6965–6971. https://doi.org/10.3748/wjg.v22.i31.6965

  43. 43

    Lee, Y.L., King, M.B., Gonzalez, R.P., et al., Blood transfusion products contain mitochondrial DNA damage-associated molecular patterns: a potential effector of transfusion-related acute lung injury, J. Surg. Res., 2014, vol. 191, no. 2, pp. 286–289. https://doi.org/10.1016/j.jss.2014.06.003

  44. 44

    Polettini, J., Behnia, F., Taylor, B.D., et al., Telomere fragment induced amnion cell senescence: a contributor to parturition?, PLoS One, 2015, vol 10. e 0137188. https://doi.org/10.1371/journal.pone.0137188

  45. 45

    Wang, L., Yu, X., and Liu, J.P., Telomere damage response and low-grade inflammation, Adv. Exp. Med. Biol., 2017, vol. 1024, pp. 213–224. https://doi.org/10.1007/978-981-10-5987-2_10

  46. 46

    Dey, S., Marino, N., and Bishop, K., A plasma telomeric cell-free DNA level in unaffected women with BRCA1 or/and BRCA2 mutations: a pilot study, Oncotarget, 2017, vol. 9, no. 3, pp. 4214–4222. https://doi.org/10.18632/oncotarget.23767

  47. 47

    Zinkova, A., Brynychova, I., Svacina, A., et al., Cell-free DNA from human plasma and serum differs in content of telomeric sequences and its ability to promote immune response, Sci. Rep., 2017, vol. 7, no. 1, p. 2591. https://doi.org/10.1038/s41598-017-02905-8

  48. 48

    Chestkov, I.V., Jestkova, E.M., Ershova, E.S., et al., Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients, Schizophr. Res., 2018, vol. 197, pp. 305–314. https://doi.org/10.1016/j.schres.2018.01.001

  49. 49

    McCarthy, C.G., Wenceslau, C.F., and Goulopoulou, S., Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats, Cardiovasc. Res., 2015, vol. 107, no. 1, pp. 119–130.

  50. 50

    https://doi.org/10.1093/cvr/cvv137

  51. 51

    Brock, G.J. and Bird, A., Mosaic methylation of the repeat unit of the human ribosomal RNA genes, Hum. Mol. Genet., 1997, vol. 6, no. 3, pp. 451–456.

  52. 52

    von Sonntag, C., Free-Radical-Induced DNA Damage and its Repair: A Chemical Perspective, Berlin: Springer-Verlag, 2006.

  53. 53

    Kostyuk, S.V., Mordkovich, N.N., Okorokova, N.A., et al., Increased transfection of the easily oxidizable GC-rich DNA fragments into the MCF7 breast cancer cell, Oxid. Med. Cell. Longev., 2019, vol. 2019, article ID 2348165.

  54. 54

    Veiko, N.N. and Spitkovskii, D.M., The accumulation of single-strand breaks does not lead to double-strand breaks in the transcribed region of the human ribosome repeat, Radiats. Biol. Radioekol., 2000, vol. 40, no. 4, pp. 396–404.

  55. 55

    Kostyuk, S.V., Ershova, E.S., Konorova, I.L., et al., Chronic exposure to ionizing radiation results in an increase of ribosomal repeat fraction in the total plasma cell-free DNA, Med. Genet., 2013, vol. 12, no. 12, pp. 20–28.

  56. 56

    Ermakov, A.V., Konkova, M.S., Kostyuk, S.V., et al., Oxidized extracellular DNA as a stress signal in human cells, Oxid. Med. Cell Longev., 2013, vol. 2013, no. 649747. https://doi.org/10.1155/2013/649747

  57. 57

    Zafiropoulos, A., Tsentelierou, E., Linardakis, M., et al., Preferential loss of 5S and 28S rDNA genes in human adipose tissue during ageing, Int. J. Biochem. Cell Biol., 2005, vol. 37, no. 2, pp. 409–415. https://doi.org/10.1016/j.biocel.2004.07.007

  58. 58

    Ershova, E., Sergeeva, V., Klimenko, M., et al., Circulating cell‑free DNA concentration and DNase I activity of peripheral blood plasma change in case of pregnancy with intrauterine growth restriction compared to normal pregnancy, Biomed. Rep., 2017, vol. 7, no. 4, pp. 319–324.

  59. 59

    Korzeneva, I.B., Kostuyk, S.V., and Ershova, L.S., Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation, Mutat. Res., 2015, vol. 779, pp. 1–15. https://doi.org/10.1016/j.mrfmmm.2015.05.004

  60. 60

    Speranskii, A.I., Kostyuk, S.V., Veiko, N.N., and Kalashnikova, E.A., Enrichment of extracellular DNA from the cultivation medium of human peripheral blood mononuclears with genomic CpG rich fragments results in increased cell production of IL-6 and TNF-a via activation of the NF-kB signaling pathway, Biochemistry(Moscow), Suppl. Ser. B: Biomed. Chem., 2015, pp. 174–184.

  61. 61

    Veiko, N.N., Egolina, N.A., Radzivil, G.G., et al., Quantitative analysis of repetitive sequences in human genomic DNA and detection of an elevated ribosomal repeat copy number in patients with schizophrenia (the results of molecular and cytogenetic analysis), Mol. Biol. (Moscow), 2003, vol. 37, pp. 349–357.

  62. 62

    Veiko, N.N., Lyapunova, N.A., Bogush, A.I., and Spitkovskii, D.M., Proteins are tightly bound with transcribed regions of human ribosomal genes, Mol. Biol. (Moscow), 1998, vol. 32, pp. 18–522.

  63. 63

    Veiko, N.N., Kostyuk, S.V., Ermakov, A.V., et al., Peripheral blood serum from healthy donors contains antibodies against the fragment of transcribed region of ribosomal repeat, Bull. Exp. Biol. Med., 2007, vol. 144, pp. 304–308.

  64. 64

    Veiko, N.N., Neverova, M.E., and Fidelina, O., The effect of CpG-rich DNA fragments on the development of hypertension in spontaneously hypertensive rats (SHR), Biochemistry(Moscow), Suppl. Ser. B: Biomed. Chem., 2010, vol. 4, pp. 269–278.

  65. 65

    Hemmi, H., Takeuchi, O., Kawai, T., et al., A Toll-like receptor recognizes bacterial DNA, Nature, 2000, vol. 408, no. 6813, pp. 740–755. https://doi.org/10.1038/35047123

  66. 66

    Kostjuk, S., Loseva, P., Chvartatskaya, O., et al., Extracellular GC-rich DNA activates TLR9- and NF-kB-dependent signaling pathways in human adipose-derived mesenchymal stem cells (haMSCs), Expert. Opin. Biol. Ther.Suppl. 1, 2012, pp. S99—S111. https://doi.org/10.1517/14712598.2012.690028

  67. 67

    Kostyuk, S.V., Porokhovnik, L.N., Ershova, E.S., et al., Changes of KEAP1/NRF2 and IKB/NF-κB expression levels induced by cell-free DNA in different cell types, Oxid. Med. Cell Longev., 2018, no. 1052413. https://doi.org/10.1155/2018/1052413

  68. 68

    Alekseeva, A.Y., Kameneva, L.V., Kostyuk, S.V., and Veiko, N.N., Reception and following ROS production in endothelial cells, Adv. Exp. Med. Biol., 2016, vol. 924, pp. 127–131. https://doi.org/10.1007/978-3-319-42044-8_25

  69. 69

    Konkova, M.S., Ermakov, A.V., Efremova, L.V., et al., Influence of X-ray and/or CpG-DNA induced oxidative stress on adaptive response in human lymphocytes, Int. J. Low Radiat., 2010, vol. 7, pp. 446—452. https://doi.org/10.1504/IJLR.2010.037667

  70. 70

    Veiko, N.N., Kalashnikova, E.A., Kokarovtseva, S.N., et al., Stimulatory effect of fragments from transcribed region of ribosomal repeat on human peripheral blood lymphocytes, Bull. Exp. Biol. Med., 2006, vol. 142, pp. 428–432.

  71. 71

    Ermakov, A.V., Konkova, M.S., Kostyuk, S.V., et al., Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation, Mutat. Res., 2009, vol. 669, nos. 1–2, pp. 155–161. https://doi.org/10.1016/j.mrfmmm.2009.06.005

  72. 72

    Kostyuk, S.V., Malinovskaya, E.M., Ermakov, A.V., et al., Fragments of cell-free DNA increase transcription in human mesenchymal stem cells, activate TLR-dependent signal pathway, and suppress apoptosis, Biochemistry(Moscow), Suppl. Ser. B: Biomed. Chem., 2012, vol. 6, pp. 68–74.

  73. 73

    Sergeeva, V.A., Kostyuk, S.V., Ershova, E.S., et al., GC-rich DNA fragments and oxidized cell-free DNA have different effects on NF-kB and NRF2 signaling in MSC, Adv. Exp. Med. Biol., 2016, vol. 924, pp. 109–112. https://doi.org/10.1007/978-3-319-42044-8_21

  74. 74

    Kostyuk, S., Smirnova, T., Kameneva, L., et al., GC-rich extracellular DNA induces oxidative stress, double-strand DNA breaks, and DNA damage response in human adipose-derived mesenchymal stem cells, Oxid. Med. Cell Longev., 2015, no. 782123.https://doi.org/10.1155/2015/782123

  75. 75

    Alekseeva, A.Yu., Bulycheva, N.V., Kostyuk, S.V., et al., Cell free DNA (cfDNA) influences nitric oxide and ros levels in human endothelial cells, in Circulating Nucleic Acids in Plasma and Serum, Gahan, P.B., Ed., Springer-Verlag, 2011, pp. 219–223.

  76. 76

    Efremova, L.V., Alekseeva, A.Y., Konkova, M.S., et al., Extracellular DNA affects NO content in human endothelial cells, Bull. Exp. Biol. Med., 2010, vol. 149, pp. 196–200.

  77. 77

    Kostyuk, S.V., Smirnova, T.D., Efremova, L.V., et al., Enhanced expression of iNOS in human endothelial cells during long-term culturing with extracellular DNA fragments, Bull. Exp. Biol. Med., 2010, vol. 149, pp. 191–195.

  78. 78

    Kostyuk, S.V., Alekseeva, A.Yu., Konkova, M.S., et al., Extracellular DNA affects the functional activity of endothelial cells, Med. Genet., 2010, vol. 9, no. 1, pp. 38–46.

  79. 79

    Bulicheva, N., Fidelina, O., Mkrtumova, N., et al., Effect of cell-free DNA of patients with cardiomyopathy and rDNA on the frequency of contraction of electrically paced neonatal rat ventricular myocytes in culture, Ann. N.Y. Acad. Sci., 2008, vol. 1137, pp. 273–277. https://doi.org/10.1196/annals.1448.023

  80. 80

    Kostyuk, S.V., Konkova, M.S., Ershova, E.S., et al., An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells, PLoS One, 2013, vol. 8. e77469. https://doi.org/10.1371/journal.pone.0077469

  81. 81

    Kostyuk, S.V., Tabakov, V.J., Chestkov, V.V., et al., Oxidized DNA induces an adaptive response in human fibroblasts, Mutat. Res., 2013, vol. 747–748, pp. 6–18. https://doi.org/10.1016/j.mrfmmm.2013.04.007

  82. 82

    Kostyuk, S.V., Alekseeva, A.Y., Kon’kova, M.S., et al., Oxidized extracellular DNA suppresses nitric oxide production by endothelial NO synthase (eNOS) in human endothelial cells (HUVEC), Bull. Exp. Biol. Med., 2014, vol. 157, pp. 202–206. https://doi.org/10.1007/s10517-014-2525-x

  83. 83

    Loseva, P., Kostyuk, S., Malinovskaya, E., et al., Extracellular DNA oxidation stimulates activation of NRF2 and reduces the production of ROS in human mesenchymal stem cells, Expert. Opin. Biol. Ther.,Suppl. 1, 2012, pp. S85–S97. https://doi.org/10.1517/14712598.2012.688948

  84. 84

    Glebova, K., Veiko, N., Kostyuk, S., et al., Oxidized extracellular DNA as a stress signal that may modify response to anticancer therapy, Cancer Lett., 2015, vol. 356, pp. 22–33. https://doi.org/10.1016/j.canlet.2013.09.005

  85. 85

    Glebova, K.V., Veiko, N.N., Nikonov, A.A., et al., Cell-free DNA as a biomarker in stroke: current status, problems and perspectives, Crit. Rev. Clin. Lab. Sci., 2018, vol. 5, no. 1, pp. 55–70. https://doi.org/10.1080/10408363.2017.1420032

  86. 86

    Brandes, R.P., Weissmann, N., and Schröder, K., Nox family NADPH oxidases: molecular mechanisms of activation, Free Radic. Biol., 2014, vol. 76, pp. 208–226. https://doi.org/10.1016/j.freeradbiomed.2014.07.046

Download references

Funding

This work was financially supported by the Russian Foundation for Basic Research (project no. 17-29-06017ofi_m) and within the State Task of the Ministry of Education and Science of the Russian Federation.

Author information

Correspondence to N. N. Veiko or S. V. Kostyuk.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Additional information

Translated by D. Novikova

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ershova, E.S., Konkova, M.S., Malinovskaya, E.M. et al. Noncanonical Functions of the Human Ribosomal Repeat. Russ J Genet 56, 30–40 (2020). https://doi.org/10.1134/S1022795420010044

Download citation

Keywords:

  • DAMPs
  • human ribosomal genes
  • rDNA
  • TLR9
  • cfDNA
  • oxidized DNA