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A topological transition from bimolecular quadruplex to G-triplex/tri-G-quadruplex exhibited by truncated double repeats of human telomere

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Abstract

Human telomeric G-rich sequences can fold back into various conformations depending upon the salt (Na+ or K+) at physiological pH. On the basis of results obtained by native PAGE electrophoresis, circular dichroism, and UV-melting experiments, we report here that truncated sequences of human telomere (d-GGGTTAGGG; GM9, d-AGGGTTAGGG; GM10, d-TAGGGTTAGGG; GM11) adopt a varied range of quadruplex conformations as a function of the cation present. By correlating CD and gel electrophoresis experiments; it was concluded that the GM9 oligonucleotide can self-associate to form a tetramer quadruplex (antiparallel; AP) in Na+ solution and a mixture of G-triplex (AP) or tri-G-quadruplex (parallel; P) along with a tetramer G-quadruplex structure (AP) in K+. The GM10 oligonucleotide formed a bimolecular G-quadruplex in both Na+ and K+ solutions, while GM11 associated to form a bimolecular G-quadruplex (AP) structure in Na+ solution and a mixture of bimolecular G-quadruplex (AP) and bimolecular G-quadruplex (P) along with parallel G-triplex or antiparallel tri-G-quadruplex in K+. All the UV-melting profiles, thermal difference spectra, and CD melting curves suggested the formation of a variety of G-quadruplex conformations by the DNA sequences studied in Na+ and K+ ions. Hypothetical models for different conformations adopted by these DNA molecules have also been proposed, which may further enhance our knowledge about the divergent topologies of guanine quadruplexes.

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References

  • Agrawal P, Hatzakis E, Guo K, Carver M, Yang D (2013) Solution structure of the major G-quadruplex formed in the human VEGF promoter in K+: insights into loop interactions of the parallel G-quadruplexes. Nucleic Acids Res 41(22):10584–10592

    Article  CAS  Google Scholar 

  • Amirbekyan K, Mansot J, Ohara K, Markarian SA, Vasseur JJ, Smietana M (2018) Template-directed excimer formation via specific non-covalent interactions between pyrene guanidinium derivatives and nucleic acids. Tetrahedron Lett 59(3):295–298

    Article  CAS  Google Scholar 

  • Balagurumoorthy P, Brahmachari SK, Mohanty D, Bansal M, Sasisekharan V (1992) Hairpin and parallel quartet structures for telomeric sequences. Nucleic Acids Res 20(15):4061–4067

    Article  CAS  Google Scholar 

  • Banihashemian SM, Periasamy V, Mohammadi SM, Ritikos R, Rahman SA (2013) Optical characterization of oligonucleotide DNA influenced by magnetic fields. Molecules 18(10):11797–11808

    Article  CAS  Google Scholar 

  • Cai H, Zhou C, Yang Q, Ai T, Huang Y, Lv Y, Geng J, Xiao D (2017) Single-molecule investigation of human telomeric G-quadruplex interactions with Thioflavin T. Chin Chem Lett 29(3):531–534

    Article  Google Scholar 

  • Chariker JH, Miller DM, Rouchka EC (2016) Computational analysis of G-quadruplex forming sequences across chromosomes reveals high density patterns near the terminal ends. PLoS One 11(10):e0165101

    Article  Google Scholar 

  • Cheng M, Zhou J, Jia G, Ai X, Mergny JL, Li C (2017) Relations between the loop transposition of DNA G-quadruplex and the catalytic function of DNAzyme. Biochim Biophys Acta (BBA) Gen Subj 1861:1913

    Article  CAS  Google Scholar 

  • Clark GR, Pytel PD, Squire CJ, Neidle S (2003) Structure of the first parallel DNA quadruplex–drug complex. J Am Chem Soc 125(14):4066–4067

    Article  CAS  Google Scholar 

  • Cutler G, Perry KM, Tjian R (1998) Adf-1 is a nonmodular transcription factor that contains a TAF-binding Myb-like motif. Mol Cell Biol 18(4):2252–2261

    Article  CAS  Google Scholar 

  • Doghaei AV, Housaindokht MR, Bozorgmehr MR (2015) Molecular crowding effects on conformation and stability of G-quadruplex DNA structure: insights from molecular dynamics simulation. J Theor Biol 7(364):103–112

    Article  Google Scholar 

  • Doidge R, Mittal S, Aslam A, Winkler GS (2012) The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex. PLoS One 7(12):e51331

    Article  CAS  Google Scholar 

  • Duskova K, Sierra S, Arias-Pérez MS, Gude L (2016) Human telomeric G-quadruplex DNA interactions of N-phenanthroline glycosylamine copper(II) complexes. Bioorg Med Chem 24(1):33–41

    Article  CAS  Google Scholar 

  • Fang G, Cech TR (1993) The β subunit of oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA. Cell 74(5):875–885

    Article  CAS  Google Scholar 

  • Jha NS, Mishra S, Mamidi AS, Mishra A, Jha SK, Surolia A (2016) Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions. RSC Adv 6(9):7474–7487

    Article  CAS  Google Scholar 

  • Kaushik M, Bansal A, Saxena S, Kukreti S (2007) Possibility of an antiparallel (tetramer) quadruplex exhibited by the double repeat of the human telomere. Biochemistry 46(24):7119–7131

    Article  CAS  Google Scholar 

  • Kaushik M, Kaushik S, Kukreti S (2016) Exploring the characterization tools of guanine-quadruplexes. Front Biosci (Landmark edition) 1(21):468–478

    Article  Google Scholar 

  • Kim MY, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley LH (2002) Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular G-quadruplex. J Am Chem Soc 124(10):2098–2099

    Article  CAS  Google Scholar 

  • Kim MY, Gleason-Guzman M, Izbicka E, Nishioka D, Hurley LH (2003) The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. Can Res 63(12):3247–3256

    CAS  Google Scholar 

  • Kolyada AK, Vaiserman AM, Krasnenkov DS (2016) Studies of telomere length in patients with Parkinson’s disease. Neurosci Behav Physiol 46(3):344–347

    Article  CAS  Google Scholar 

  • Kypr J, Kejnovská I, Renčiuk D, Vorlíčková M (2009) Circular dichroism and conformational polymorphism of DNA. Nucleic Acids Res 37(6):1713–1725

    Article  CAS  Google Scholar 

  • Lauria A, Terenzi A, Bartolotta R, Bonsignore R, Perricone U, Tutone M, Martorana A, Barone G, Almerico Maria A (2014) Does ligand symmetry play a role in the stabilization of DNA G-quadruplex host-guest complexes? Curr Med Chem 21(23):2665–2690

    Article  CAS  Google Scholar 

  • Li F, Zhou J, Xu M, Yuan G (2016) Investigation on the formation, conversion and bioactivity of a G-quadruplex structure in the PALB2 gene. Int J Biol Macromol 29(83):242–248

    Article  Google Scholar 

  • Li F, Zhou J, Xu M, Yuan G (2018a) Exploration of G-quadruplex function in c-Myb gene and its transcriptional regulation by topotecan. Int J Biol Macromol 1(107):1474–1479

    Article  Google Scholar 

  • Li S, Liu C, Gong H, Chen C, Chen X, Cai C (2018b) Simple G-quadruplex-based 2-aminopurine fluorescence probe for highly sensitive and amplified detection of microRNA-21. Talanta 1(178):974–979

    Article  Google Scholar 

  • Lim KW, Amrane S, Bouaziz S, Xu W, Mu Y, Patel DJ, Luu KN, Phan AT (2009) Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers. J Am Chem Soc 131(12):4301–4309

    Article  CAS  Google Scholar 

  • Lim KW, Ng VC, Martín-Pintado N, Heddi B, Phan AT (2013) Structure of the human telomere in Na+ solution: an antiparallel (2 + 2) G-quadruplex scaffold reveals additional diversity. Nucleic Acids Res 41(22):10556–10562

    Article  CAS  Google Scholar 

  • Limongelli V, De Tito S, Cerofolini L, Fragai M, Pagano B, Trotta R, Cosconati S, Marinelli L, Novellino E, Bertini I, Randazzo A (2013) The G-triplex DNA. Angew Chem Int Ed 52(8):2269–2273

    Article  CAS  Google Scholar 

  • Lin C, Yang D (2017) Human telomeric G-quadruplex structures, and G-quadruplex-interactive compounds. Telomeres Telomerase Methods Protoc 1587:171–196

    Article  CAS  Google Scholar 

  • Liu H, Wang YS, Tang X, Yang HX, Chen SH, Zhao H, Liu SD, Zhu YF, Wang XF, Huang YQ (2016) A novel fluorescence aptasensor for 8-hydroxy-2′-deoxyguanosine based on the conformational switching of K+-stabilized G-quadruplex. J Pharm Biomed Anal 25(118):177–182

    Article  CAS  Google Scholar 

  • Luca AD, Sacchetta P, Nieddu M, Ilio CD, Favaloro B (2007) Important roles of multiple Sp1 binding sites and epigenetic modifications in the regulation of the methionine sulfoxidereductase B1 (MsrB1) promoter. BMC Mol Biol 8:39

    Article  Google Scholar 

  • Malgowska M, Gudanis D, Kierzek R, Wyszko E, Gabelica V, Gdaniec Z (2014) Distinctive structural motifs of RNA G-quadruplexes composed of AGG, CGG and UGG trinucleotide repeats. Nucleic Acids Res 42(15):10196–10207

    Article  CAS  Google Scholar 

  • Mergny JL, Li J, Lacroix L, Amrane S, Chaires JB (2005) Thermal difference spectra: a specific signature for nucleic acid structures. Nucleic Acids Res 33(16):e138

    Article  Google Scholar 

  • Musso L, Mazzini S, Rossini A, Castagnoli L, Scaglioni L, Artali R, Di Nicola M, Zunino F, Dallavalle S (2018) c-MYC G-quadruplex binding by the RNA polymerase I inhibitor BMH-21 and analogues revealed by a combined NMR and biochemical Approach. Biochim Biophys Acta (BBA) Gen Subj 1862(3):615–629

    Article  CAS  Google Scholar 

  • Onel B, Lin C, Yang D (2014) DNA G-quadruplex and its potential as an anticancer drug target. Sci China Chemis 57(12):1605–1614

    Article  CAS  Google Scholar 

  • Ouellette MM, Wright WE, Shay JW (2011) Targeting telomerase-expressing cancer cells. J Cell Mol Med 15(7):1433–1442

    Article  CAS  Google Scholar 

  • Parkinson GN, Lee MP, Neidle S (2002) Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 417(6891):876

    Article  CAS  Google Scholar 

  • Piazza A, Cui X, Adrian M, Samazan F, Heddi B, Phan AT, Nicolas AG (2017) Non-canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae. eLife 6:e26884. https://doi.org/10.7554/eLife.26884

    Article  PubMed  PubMed Central  Google Scholar 

  • Pirh R, Šket P, Plavec J (2011) NMR study of a potential role of anions on folding of dimeric G-quadruplex in aqueous solution. Collect Symp Ser 12:226–229

    Article  CAS  Google Scholar 

  • Rachwal PA, Findlow IS, Werner JM, Brown T, Fox KR (2007) Intramolecular DNA quadruplexes with different arrangements of short and long loops. Nucleic Acids Res 35(12):4214–4222

    Article  CAS  Google Scholar 

  • Ramos-Alemán F, González-Jasso E, Pless RC (2018) Use of alternative alkali chlorides in RT and PCR of polynucleotides containing G quadruplex structures. Anal Biochem 15(543):43–50

    Article  Google Scholar 

  • Ray S, Bandaria JN, Qureshi MH, Yildiz A, Balci H (2014) G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding. Proc Natl Acad Sci 111(8):2990–2995

    Article  CAS  Google Scholar 

  • Shalaby T, Fiaschetti G, Nagasawa K, Shin-Ya K, Baumgartner M, Grotzer M (2013) G-quadruplexes as potential therapeutic targets for embryonal tumors. Molecules 18(10):12500–12537

    Article  CAS  Google Scholar 

  • Šket P, Črnugelj M, Plavec J (2005) Identification of mixed di-cation forms of G-quadruplex in solution. Nucleic Acids Res 33(11):3691–3697

    Article  Google Scholar 

  • Stefanovic S, DeMarco BA, Underwood A, Williams KR, Bassell GJ, Mihailescu MR (2015) Fragile X mental retardation protein interactions with a G quadruplex structure in the 3′-untranslated region of NR2B mRNA. Mol Biosyst 11(12):3222–3230

    Article  CAS  Google Scholar 

  • Stegle O, Payet L, Mergny JL, MacKay DJ, Huppert JL (2009) Predicting and understanding the stability of G-quadruplexes. Bioinformatics 25(12):i374–i1382

    Article  CAS  Google Scholar 

  • Sun H, Chen H, Zhang X, Liu Y, Guan A, Li Q, Yang Q, Shi Y, Xu S, Tang Y (2016) Colorimetric detection of sodium ion in serum based on the G-quadruplex conformation related DNAzyme activity. Anal Chim Acta 17(912):133–138

    Article  Google Scholar 

  • Tan W, Yi L, Zhu Z, Zhang L, Zhou J, Yuan G (2018) Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4 +, molecular crowding environment and jatrorrhizine derivatives. Talanta 1(179):337–343

    Article  Google Scholar 

  • Vasko T, Kaifie A, Stope MB, Kraus T, Ziegler P (2017) Telomeres and telomerase in hematopoietic dysfunction: prognostic implications and pharmacological interventions. Int J Mol Sci 18(11):2267

    Article  Google Scholar 

  • Welsh SJ, Dale AG, Lombardo CM, Valentine H, De La Fuente M, Schatzlein A, Neidle S (2013) Inhibition of the hypoxia-inducible factor pathway by a G-quadruplex binding small molecule. Sci Rep 3:2799

    Article  Google Scholar 

  • Xiao CD, Ishizuka T, Xu Y (2017) Antiparallel RNA G-quadruplex formed by human telomere RNA containing 8-bromoguanosine. Sci Rep 7(1):6695

    Article  Google Scholar 

  • Xing H, Gu W, Xu D, Tian F, Yao L, Wang Z, Hu X (2018) A simple fluorescent assay for cyromazine detection in raw milk by using CYR-stabilized G-quadruplex formation. RSC Adv 8(5):2418–2425

    Article  CAS  Google Scholar 

  • Xu Y, Noguchi Y, Sugiyama H (2006) The new models of the human telomere d [AGGG (TTAGGG) 3] in K+ solution. Bioorg Med Chem 14(16):5584–5591

    Article  CAS  Google Scholar 

  • Xu Y, Ishizuka T, Yang J, Ito K, Katada H, Komiyama M, Hayashi T (2012) Oligonucleotide models of telomeric DNA and RNA form a Hybrid G-quadruplex structure as a potential component of telomeres. J Biol Chem 287(50):41787–41796

    Article  CAS  Google Scholar 

  • Zhang N, Phan AT, Patel DJ (2005) (3 + 1) Assembly of three human telomeric repeats into an asymmetric dimeric G-quadruplex. J Am Chem Soc 127(49):17277–17285

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the University of Delhi for its R&D Grants. Financial support by the Council of Scientific and Industrial Research to Mohan Kumar is gratefully acknowledged.

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Authors and Affiliations

  1. Nucleic Acid Research Laboratory, Department of Chemistry, University of Delhi, Delhi, India

    Mohan Kumar, Mahima Kaushik & Shrikant Kukreti

  2. Cluster Innovation Centre, University of Delhi, Delhi, India

    Mahima Kaushik

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  1. Mohan Kumar
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  2. Mahima Kaushik
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Correspondence to Shrikant Kukreti.

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Kumar, M., Kaushik, M. & Kukreti, S. A topological transition from bimolecular quadruplex to G-triplex/tri-G-quadruplex exhibited by truncated double repeats of human telomere. Eur Biophys J 47, 903–915 (2018). https://doi.org/10.1007/s00249-018-1312-4

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