Skip to main content
SpringerLink
Log in

Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. II. The putative role of G-quadruplex structures in genomic rearrangements

  • Published:
Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract

Three evolutionary conserved (G-rich) sites of Alu repeats (PQS2, PQS3, and PQS4) could form in vitro stable inter- and intramolecular G-quadruplexes (GQs). Structures and topologies of these GQs were elucidated using spectral methods. The study of self-association of G-rich Alu fragments performed using a FRET-based method revealed dimeric GQ formation from two distally located sites (PQS2)2, (PQS3)2 or PQS2−PQS3 within one extended single stranded DNA. Using DOSY NMR, AFM microscopy and differential CD spectroscopy it has been demonstrated that oligomer PQS4 (folded into a parallel intramolecular GQ) forms stacks of quadruplexes stabilized by stacking interactions of external G-tetrads. Comparative analysis of the properties of various GQs suggests involvement of two universal general mechanisms of GQ-dependent genomic rearrangements: (i) formation of dimeric GQs from fragments of different molecules; (ii) formation of GQ-GQ-stacks from pre-folded intramolecular parallel GQs from different strands. Thus, association of G-rich Alu motifs with sensitivity to double-strand breaks and rearrangements may be attributed not to structural features of G-rich Alu fragments, but also to their high abundance.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Loomis, E.W., Sanz, L.A., Chedin, F., and Hagerman, P.J., PLoS Genet., 2014, vol. 10, e1004294. PGENETICS-D-13-02486 [pii] doi 10.1371/journal. pgen.1004294

    Article  Google Scholar 

  2. Murat, P., Zhong, J., Lekieffre, L., Cowieson, N.P., Clancy, J.L., Preiss, T., Balasubramanian, S., Khanna, R., and Tellam, J., Nat. Chem. Biol., 2014, vol. 10, pp. 358–364. nchembio.1479 [pii] doi 10.1038/nchembio.1479

    Article  CAS  Google Scholar 

  3. Harris, L.M. and Merrick, C.J., PLoS Pathog., 2015, vol. 11, e1004562. PPATHOGENS-D-14-01954 [pii] doi 10.1371/journal.ppat.1004562

    Article  Google Scholar 

  4. Cahoon, L.A. and Seifert, H.S., Science, 2009, vol. 325, pp. 764–767. 325/5941/764 [pii] doi 10.1126/science.1175653

    Article  CAS  Google Scholar 

  5. Metifiot, M., Amrane, S., Litvak, S., and Andreola, M.L., Nucleic Acids Res., 2014, vol. 42, pp. 12352–12366. gku999 [pii] doi 10.1093/nar/gku999

    Article  CAS  Google Scholar 

  6. Javadekar, S.M. and Raghavan, S.C., FEBS J., 2015, vol. 282, pp. 2627–2645. doi 10.1111/febs.13311

    Article  CAS  Google Scholar 

  7. Sekridova, A.V., Varizhuk, A.M., Tatarinova, O.N., Severov, V.V., Barinov, N.A., Smirnov, I.P., Lazarev, V.N., Klinov, D.V., and Pozmogova, G.E., Biomed. Khim., 2016, vol. 62, pp. 535–543.

    Article  CAS  Google Scholar 

  8. 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. 2007.02.002

    Article  CAS  Google Scholar 

  9. Batzer, M.A. and Deininger, P.L., Nat. Rev. Genet., 2002, vol. 3, pp. 370–379. nrg798 [pii] doi 10.1038/nrg798

    Article  CAS  Google Scholar 

  10. 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/s11171-008-1010-6

    Google Scholar 

  11. Ackermann, D., Rasched, G., Verma, S., Schmidt, T.L., Heckel, A., and Famulok, M., Chem. Commun. (Camb.), 2010, vol. 46, pp. 4154–4156. doi 10.1039/c0cc00390e

    Article  CAS  Google Scholar 

  12. Besschetnova, I.A., Pozmogova, G.E., Chuvilin, A.N., Shchelkina, A.K., and Borisova, O.F., Mol. Biol. (Moscow), 2006, vol. 40, pp. 489–496.

    Article  CAS  Google Scholar 

  13. Abu-Ghazalah, R.M., Irizar, J., Helmy, A.S., and Macgregor, R.B., Jr., Biophys. Chem., 2013, vol. 147, pp. 123–129. S0301-4622(10)00004-9 [pii] doi 10.1016/j.bpc.2010.01.003

    Article  Google Scholar 

  14. Konkel, M.K. and Batzer, M.A., Semin. Cancer Biol., 2010, vol. 20, pp. 211–221. S1044-579X(10)00009-X [pii] doi 10.1016/j.semcancer.2010.03.001

    Article  CAS  Google Scholar 

  15. Do, N.Q., Lim, K.W., Teo, M.H., Heddi, B., and Phan, A.T., Nucleic Acids Res., 2011, vol. 39, pp. 9448–9457. gkr539 [pii] doi 10.1093/nar/gkr539

    Article  CAS  Google Scholar 

  16. Tothova, P., Krafcikova, P., and Viglasky, V., Biochemistry, 2014, vol. 53, pp. 7013–7027. doi 10.1021/bi500773c

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Federal Research and Clinical Center of Physical-Chemical Medicine, ul. Malaya Pirogovskaya, 1a, Moscow, 119435, Russia

    A. M. Varizhuk, A. V. Sekridova, M. V. Tankevich, V. S. Podgorsky, I. P. Smirnov & G. E. Pozmogova

Authors
  1. A. M. Varizhuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Sekridova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. V. Tankevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. S. Podgorsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. P. Smirnov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. E. Pozmogova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. E. Pozmogova.

Additional information

Original Russian Text © A.M. Varizhuk, A.V. Sekridova, M.V. Tankevich, V.S. Podgorsky, I.P. Smirnov, G.E. Pozmogova, 2017, published in Biomeditsinskaya Khimiya.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Varizhuk, A.M., Sekridova, A.V., Tankevich, M.V. et al. Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. II. The putative role of G-quadruplex structures in genomic rearrangements. Biochem. Moscow Suppl. Ser. B 11, 146–153 (2017). https://doi.org/10.1134/S1990750817020093

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990750817020093

Keywords

Search

Navigation