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.
Similar content being viewed by others
References
Hoffman, Y., Pilpel, Y., and Oren, M., J. Mol. Cell. Biol., 2014, vol. 6, pp. 192–197. mju020 [pii] doi 10.1093/jmcb/mju020
Cui, F., Sirotin, M.V., and Zhurkin, V.B., Biol. Direct., 2011, vol. 6, p. 2. 1745-6150-6-2 [pii] doi 10.1186/1745-6150-6-2
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/ddt569
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.0101607
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/btt044
Batzer, M.A. and Deininger, P.L., Nat. Rev. Genet., 2002, vol. 3, pp. 370–379. [pii] doi 10.1038/nrg798
Chen, L.L. and Carmichael, G.G., Cell Cycle, 2008, vol. 7, pp. 3294–3301. 6927 [pii]
Kleinberger, Y. and Eisenberg, E., BMC Genomics, 2010, vol. 11, p. 453. 1471-2164-11-453 [pii] doi 10.1186/1471-2164-11-453
Wahlstedt, H. and Ohman, M., Wiley Interdiscip. Rev. RNA, 2011, vol. 2, pp. 761–771. doi 10.1002/wrna.89
Mallela, A. and Nishikura, K., Crit. Rev. Biochem. Mol. Biol., 2012, vol. 47, pp. 493–501. doi 10.3109/10409238.2012.714350
Nishikura, K., Nat. Rev. Mol. Cell. Biol., 2015. nrm.2015.4 [pii] doi 10.1038/nrm.2015.4
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.2012.10.005
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.M114.567073
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 10.1186/1471-2164-15-677
Kejnovsky, E., Tokan, V., and Lexa, M., Chromosome Res., 2015, vol. 23, pp. 615–623. [pii] doi 10.1007/s10577-015-9491-7
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.2015.30
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
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
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.
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.0089383
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]
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.1516925112
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.2015.05.020
Luo, Y., Lu, X., and **e, H., Biomed. Res. Int., 2014, vol. 2014, p. 784706. doi 10.1155/2014/784706
Grandi, F.C. and An, W., Mob. Genet. Elements, 2013, vol. 3, e25674. 2013MGE0003R [pii] doi 10.4161/mge.25674
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.2012.04.019
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.2011.10.010
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/gkp898
Husby, J., Todd, A.K., Platts, J.A., and Neidle, S., Biopolymers, 2013, vol. 99, pp. 989–1005. doi 10.1002/bip.22340
Mela, I., Kranaster, R., Henderson, R.M., Balasubramanian, S., and Edwardson, J.M., Biochemistry, 2012, vol. 51, pp. 578–585. doi 10.1021/bi201600g
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/gkt957
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. 2015.06.016
Rivetti, C. and Codeluppi, S., Ultramicroscopy, 2001, vol. 87, pp. 55–66.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © 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, 2017, published in Biomeditsinskaya Khimiya.
Rights and permissions
About this article
Cite this article
Sekridova, A.V., Varizhuk, A.M., Tatarinova, O.N. et al. Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. I. Noncanonical structures. Biochem. Moscow Suppl. Ser. B 11, 62–71 (2017). https://doi.org/10.1134/S1990750817010097
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990750817010097