Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. I. Noncanonical structures

  • A. V. Sekridova
  • A. M. Varizhuk
  • O. N. Tatarinova
  • V. V. Severov
  • N. A. Barinov
  • I. P. Smirnov
  • V. N. Lazarev
  • D. V. Klinov
  • G. E. Pozmogova
Article
  • 23 Downloads

Abstract

We report results of the first systematic study of conformational polymorphism of G-rich DNA fragments of Alu-repeats. Alu retrotransposons are primate-specific short interspersed elements. Using the Alu sequence of the prooncogen bcl2 intron and the consensus AluSx sequence as representative examples, we have determined characteristic Alu sites that are capable of adopting G-quadruplex (GQ) conformations (i.e., potential quadruplex sites—PQSAlu), and demonstrated by bioinformatics methods that these sites are Alu-specific in the human genome. Genomic frequencies of PQSAlu were assessed (~1/10000 bp). These sites were found to be characteristic of young (active) Alu families (Alu-Y). A recombinant DNA sequence bearing the Alu element of the human bcl2 gene (304 bp) and its PQS-mutant (Alu-PQS) were constructed. The formation of noncanonical structures in Alubcl2 dsDNA and their absence in the case of Alu-PQS have been shown using DMS-footprinting and atomic force microscopy (AFM). Expression vectors bearing wild-type and mutant Alu insertions in the promoter regions of the reporter gene have been prepared, and their regulatory effects have been compared during transfection of НЕК293 and HeLa cells. We suggest that the dynamic study of the spatial organization of Alu repeats may provide insight into the mechanisms of genomic rearrangements responsible for the development of many oncological and neurodegenerative diseases.

Keywords

G-quadruplex DNA Alu-repeats dynamics of DNA secondary structures 

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References

  1. 1.
    Hoffman, Y., Pilpel, Y., and Oren, M., J. Mol. Cell. Biol., 2014, vol. 6, pp. 192–197. mju020 [pii] doi 10.1093/jmcb/mju020CrossRefGoogle Scholar
  2. 2.
    Cui, F., Sirotin, M.V., and Zhurkin, V.B., Biol. Direct., 2011, vol. 6, p. 2. 1745-6150-6-2 [pii] doi 10.1186/1745-6150-6-2CrossRefGoogle Scholar
  3. 3.
    Spengler, R.M., Oakley, C.K., and Davidson, B.L., Hum. Mol. Genet., 2014, vol. 23, pp. 1783–1793. ddt569 [pii] doi 10.1093/hmg/ddt569CrossRefGoogle Scholar
  4. 4.
    Bose, P., Hermetz, K.E., Conneely, K.N., and Rudd, M.K., PLoS One, 2014, vol. 9, e101607. PONED-14-14652 [pii] doi 10.1371/journal.pone.0101607CrossRefGoogle Scholar
  5. 5.
    Hoffman, Y., Dahary, D., Bublik, D.R., Oren, M., and Pilpel, Y., Bioinformatics, 2013, vol. 29, pp. 894–902. btt044 [pii] doi 10.1093/bioinformatics/btt044CrossRefGoogle Scholar
  6. 6.
    Batzer, M.A. and Deininger, P.L., Nat. Rev. Genet., 2002, vol. 3, pp. 370–379. [pii] doi 10.1038/nrg798CrossRefGoogle Scholar
  7. 7.
    Chen, L.L. and Carmichael, G.G., Cell Cycle, 2008, vol. 7, pp. 3294–3301. 6927 [pii]CrossRefGoogle Scholar
  8. 8.
    Kleinberger, Y. and Eisenberg, E., BMC Genomics, 2010, vol. 11, p. 453. 1471-2164-11-453 [pii] doi 10.1186/1471-2164-11-453CrossRefGoogle Scholar
  9. 9.
    Wahlstedt, H. and Ohman, M., Wiley Interdiscip. Rev. RNA, 2011, vol. 2, pp. 761–771. doi 10.1002/wrna.89CrossRefGoogle Scholar
  10. 10.
    Mallela, A. and Nishikura, K., Crit. Rev. Biochem. Mol. Biol., 2012, vol. 47, pp. 493–501. doi 10.3109/10409238.2012.714350CrossRefGoogle Scholar
  11. 11.
    Nishikura, K., Nat. Rev. Mol. Cell. Biol., 2015. nrm.2015.4 [pii] doi 10.1038/nrm.2015.4Google Scholar
  12. 12.
    Saini, N., Zhang, Y., Usdin, K., and Lobachev, K.S., Biochimie, 2013, vol. 95, pp. 117–123. S0300-9084(12)00405-1 [pii] doi 10.1016/j.biochi.2012.10.005CrossRefGoogle Scholar
  13. 13.
    Bharti, S.K., Sommers, J.A., Zhou, J., Kaplan, D.L., Spelbrink, J.N., Mergny, J.L., and Brosh, R.M., Jr., J. Biol. Chem., 2014, vol. 289, pp. 29975–29993. M114.567073 [pii] doi 10.1074/jbc.M114.567073CrossRefGoogle Scholar
  14. 14.
    Dong, D.W., Pereira, F., Barrett, S.P., Kolesar, J.E., Cao, K., Damas, J., Yatsunyk, L.A., Johnson, F.B., and Kaufman, B.A., BMC Genomics, 2014, vol. 15, p. 677. 1471-2164-15-677 [pii] doi 10.1186/1471-2164-15-677CrossRefGoogle Scholar
  15. 15.
    Kejnovsky, E., Tokan, V., and Lexa, M., Chromosome Res., 2015, vol. 23, pp. 615–623. [pii] doi 10.1007/s10577-015-9491-7CrossRefGoogle Scholar
  16. 16.
    Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W.W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., and Rehm, H.L., Genet. Med., 2015, vol. 17, pp. 405–424. gim201530 [pii] doi 10.1038/gim.2015.30CrossRefGoogle Scholar
  17. 17.
    Kriegs, J.O., Churakov, G., Jurka, J., Brosius, J., and Schmitz, J., Trends Genet., 2007, vol. 23, pp. 158–161. S0168-9525(07)00037-6 [pii] doi 10.1016/j.tig.2007.02.002CrossRefGoogle Scholar
  18. 18.
    Luk’yanova, T.A., Zaitseva, M.A., Karpov, V.A., and Pozmogova, G.E., Bioorgan. Khim., 2008, vol. 34, pp. 83–88. doi 10.1007/s11171-008-1010-6Google Scholar
  19. 19.
    Tatarinova, O.N., Luk’yanova, T.N., Zaitseva, M.A., Veremeev, K.Yu., Karpov, V.A., Chuvilin, A.N., Petrunin, D.D., and Pozmogova, G.E., Byull. Eksper. Biol. Med., 2008, vol. 145, pp. 280–284.CrossRefGoogle Scholar
  20. 20.
    Tatarinova, O., Tsvetkov, V., Basmanov, D., Barinov, N., Smirnov, I., Timofeev, E., Kaluzhny, D., Chuvilin, A., Klinov, D., Varizhuk, A., and Pozmogova, G., PLoS One, 2014, vol. 9, e89383. PONED-13-39549 [pii] doi 10.1371/journal.pone.0089383CrossRefGoogle Scholar
  21. 21.
    Klinov, D.V., Lagutina, I.V., Prokhorov, V.V., Neretina, T., Khil, P.P., Lebedev, Y.B., Cherny, D.I., Demin, V.V., and Sverdlov, E.D., Nucl. Acids Res., 1998, vol. 26, pp. 4603–4610. gkb752 [pii]CrossRefGoogle Scholar
  22. 22.
    Li, X.M., Zheng, K.W., Zhang, J.Y., Liu, H.H., He, Y.D., Yuan, B.F., Hao, Y.H., and Tan, Z., Proc. Natl. Acad. Sci. USA, 2015, vol. 112, pp. 14581–14586. 1516925112 [pii] doi 10.1073/pnas.1516925112CrossRefGoogle Scholar
  23. 23.
    Daniel, C., Lagergren, J., and Ohman, M., Biochimie, 2015, vol. 117, pp. 22–27. S0300-9084(15)00170-4 [pii] doi 10.1016/j.biochi.2015.05.020CrossRefGoogle Scholar
  24. 24.
    Luo, Y., Lu, X., and Xie, H., Biomed. Res. Int., 2014, vol. 2014, p. 784706. doi 10.1155/2014/784706Google Scholar
  25. 25.
    Grandi, F.C. and An, W., Mob. Genet. Elements, 2013, vol. 3, e25674. 2013MGE0003R [pii] doi 10.4161/mge.25674CrossRefGoogle Scholar
  26. 26.
    Burns, K.H. and Boeke, J.D., Cell, 2012, vol. 149, pp. 740–752. S0092-8674(12)00517-X [pii] doi 10.1016/j.cell.2012.04.019CrossRefGoogle Scholar
  27. 27.
    Cheng, L.C., Pai, T.W., and Li, L.A., Steroids, 2012, vol. 77, pp. 100–109. S0039-128X(11)00314-X [pii] doi 10.1016/j.steroids.2011.10.010CrossRefGoogle Scholar
  28. 28.
    Zheng, K.W., Chen, Z., Hao, Y.H., and Tan, Z., Nucl. Acids Res., 2010, vol. 38, pp. 327–338. gkp898 [pii] doi 10.1093/nar/gkp898CrossRefGoogle Scholar
  29. 29.
    Husby, J., Todd, A.K., Platts, J.A., and Neidle, S., Biopolymers, 2013, vol. 99, pp. 989–1005. doi 10.1002/bip.22340Google Scholar
  30. 30.
    Mela, I., Kranaster, R., Henderson, R.M., Balasubramanian, S., and Edwardson, J.M., Biochemistry, 2012, vol. 51, pp. 578–585. doi 10.1021/bi201600gCrossRefGoogle Scholar
  31. 31.
    Henderson, A., Wu, Y., Huang, Y.C., Chavez, E.A., Platt, J., Johnson, F.B., Brosh, R.M., Jr., Sen, D., and Lansdorp, P.M., Nucl. Acids Res., 2014, vol. 42, pp. 860–869. gkt957 [pii] doi 10.1093/nar/gkt957CrossRefGoogle Scholar
  32. 32.
    Ma, D.L., Zhang, Z., Wang, M., Lu, L., Zhong, H.J., and Leung, C.H., Chem. Biol., 2015, vol. 22, pp. 812–828. S1074-5521(15)00242-2 [pii] doi 10.1016/j.chembiol. 2015.06.016CrossRefGoogle Scholar
  33. 33.
    Rivetti, C. and Codeluppi, S., Ultramicroscopy, 2001, vol. 87, pp. 55–66.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • A. V. Sekridova
    • 1
  • A. M. Varizhuk
    • 1
  • O. N. Tatarinova
    • 1
  • V. V. Severov
    • 1
  • N. A. Barinov
    • 1
  • I. P. Smirnov
    • 1
  • V. N. Lazarev
    • 1
  • D. V. Klinov
    • 1
  • G. E. Pozmogova
    • 1
  1. 1.Federal Research and Clinical Center of Physical-Chemical MedicineMoscowRussia

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