Effects of Protein Binding on DNA G-Quadruplex Structures

(*) Corresponding author

Authors' affiliations

DOI's assignment:
the author of the article can submit here a request for assignment of a DOI number to this resource!
Cost of the service: euros 10,00 (for a DOI)


The non-canonical G-quadruplex is a unique DNA structure that has received widespread attention because of its potential functions not only in vitro but also in vivo. The G-quadruplex is stabilized by formation of Hoogsteen hydrogen bonds in guanine quartets and involves cation coordination and dehydration. Although a number of proteins have been identified that specifically stabilize and destabilize G-quadruplexes, the effect of the protein binding remains unclear. Here, we review the behaviors of proteins binding to G-quadruplexes. We also discuss analyses of the thermodynamic and binding properties of G-quadruplexes in the complexes formed by histones and thrombins. These studies have helped us to understand the essential features of interaction between G-quadruplexes and proteins
Copyright © 2011 Praise Worthy Prize - All rights reserved.


DNA G-quadruplexes; Proteins; Electrostatic Interactions; Loop Interactions; Hydration

Full Text:



J. Zhao, A. Bacolla, G. Wang, and K.M. Vasquez, Non-B DNA structure-induced genetic instability and evolution, Cell Mol. Life Sci., Volume 67, 2010, Pages 43-62.

P.C. Bevilacqua, and J.M. Blose, Structures, kinetics, thermodynamics, and biological functions of RNA hairpins, Annu. Rev. Phys. Chem., Volume 59, 2008, Pages 79-103.

S.M. Mirkin, Expandable DNA repeats and human disease, Nature, Volume 447, 2007, Pages 932-940.

R.V. Brown, and L.H. Hurley, DNA acting like RNA, Biochem. Soc. Trans., Volume 39, 2011, Pages 635-640.

J. Liu, Z. Cao, and Y. Lu, Functional nucleic acid sensors, Chem. Rev., Volume 109, 2009, Pages 1948-1998.

C. Teller, and I. Willner, Functional nucleic acid nanostructures and DNA machines, Curr. Opin. Biotechnol., Volume 21, 2010, Pages 376-391.

B. Gatto, M. Palumbo, and C. Sissi, Nucleic acid aptamers based on the G-quadruplex structure: therapeutic and diagnostic potential, Curr. Med. Chem., Volume 16, 2009, Pages 1248-1265.

M. Egli, and P.S. Pallan, The many twists and turns of DNA: template, telomere, tool, and target, Curr. Opin. Struct. Biol., Volume 20, 2010, Pages 262-275.

D. Miyoshi, and N. Sugimoto, Molecular crowding effects on structure and stability of DNA, Biochimie, Volume 90, 2008, Pages 1040-1051.

D. Miyoshi, and N. Sugimoto, G-Quartet, G-Quadruplex, and G-Wire Regulated by Chemical Stimuli, Methods Mol. Biol., Volume 749, 2011, Pages 93-104.

D. Yang, and K. Okamoto, Structural insights into G-quadruplexes: towards new anticancer drugs, Future Med. Chem., Volume 2, 2010, Pages 619-646.

S. Balasubramanian, L.H. Hurley, and S. Neidle, Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?, Nat. Rev. Drug. Discov., Volume 10, 2011, Pages 261-275.

Y. Xu, Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA, Chem. Soc. Rev., Volume 40, 2011, Pages 2719-2740.

B. Juskowiak, and S. Takenaka, Fluorescence resonance energy transfer in the studies of guanine quadruplexes, Methods Mol. Biol., Volume 335, 2006, Pages 311-341.

J.T. Davis, and G.P. Spada, Supramolecular architectures generated by self-assembly of guanosine derivatives, Chem. Soc. Rev., Volume 36, 2007, Pages 296-313.

M. Gellert, M.N. Lipsett, and D.R. Davies, Helix formation by guanylic acid, Proc. Natl. Acad. Sci. U. S. A., Volume 48, 1962, Pages 2013-2018.

J.R. Williamson, M.K. Raghuraman, and T.R. Cech, Monovalent cation-induced structure of telomeric DNA: the G-quartet model, Cell, Volume 59, 1989, Pages 871-880.

F.W. Smith, and J. Feigon, Quadruplex structure of Oxytricha telomeric DNA oligonucleotides, Nature, Volume 356, 1992, Pages 164-168.

A.N. Lane, J.B. Chaires, R.D. Gray, and J.O. Trent, Stability and kinetics of G-quadruplex structures, Nucleic Acids Res., Volume 36, 2008, Pages 5482-515.

M.A. Keniry, Quadruplex structures in nucleic acids, Biopolymers, Volume 56, 2000, Pages 123-146.

M.C. Miller, R. Buscaglia, J.B. Chaires, A.N. Lane, and J.O. Trent, Hydration Is a Major Determinant of the G-Quadruplex Stability and Conformation of the Human Telomere 3' Sequence of d(AG(3)(TTAG(3))(3)), J. Am. Chem. Soc., Volume 132, 2010, Pages 17105-17107.

S. Neidle, Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer, FEBS J., Volume 277, 2010, Pages 1118-1125.

S. Neidle, The structures of quadruplex nucleic acids and their drug complexes, Curr. Opin. Struct. Biol., Volume 19, 2009, Pages 239-250.

D. Monchaud, and M.P. Teulade-Fichou, A hitchhiker's guide to G-quadruplex ligands, Org. Biomol. Chem., Volume 6, 2008, Pages 627-636.

T.M. Ou, Y.J. Lu, J.H. Tan, Z.S. Huang, K.Y. Wong, and L.Q. Gu, G-quadruplexes: targets in anticancer drug design, ChemMedChem, Volume 3, 2008, Pages 690-713.

A. De Cian, L. Lacroix, C. Douarre, N. Temime-Smaali, C. Trentesaux, J.F. Riou, and J.L. Mergny, Targeting telomeres and telomerase, Biochimie, Volume 90, 2008, Pages 131-155.

K. Padmanabhan, and A. Tulinsky, An ambiguous structure of a DNA 15-mer thrombin complex, Acta Crystallog. Section D, Volume 52, 1996, Pages 272-282.

M.P. Horvath, and S.C. Schultz, DNA G-quartets in a 1.86 A resolution structure of an Oxytricha nova telomeric protein-DNA complex, J. Mol. Biol., Volume 310, 2001, Pages 367-377.

K. Takahama, K. Kino, S. Arai, R. Kurokawa, and T. Oyoshi, Identification of Ewing's sarcoma protein as a G-quadruplex DNA- and RNA-binding protein, FEBS J., Volume 278, 2011, Pages 988-998.

V. Gonzalez, and L.H. Hurley, The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity, Biochemistry, Volume 49, 2010, Pages 9706-9714.

H.J. Lipps, and D. Rhodes, G-quadruplex structures: in vivo evidence and function, Trends Cell Biol., Volume 19, 2009, Pages 414-422.

H.M. Wong, L. Payet, and J.L. Huppert, Function and targeting of G-quadruplexes, Curr. Opin. Mol. Ther., Volume 11, 2009, Pages 146-155.

M. Fry, Tetraplex DNA and its interacting proteins, Front. Biosci., Volume 12, 2007, Pages 4336-4351.

T.M. Bryan, and M.B. Jarstfer, Interrogation of G-quadruplex-protein interactions, Methods, Volume 43, 2007, Pages 332-339.

C. Sissi, B. Gatto, and M. Palumbo, The evolving world of protein-G-quadruplex recognition: A medicinal chemist's perspective, Biochimie, Volume 93, 2011, Pages 1219-1230.

K. Paeschke, T. Simonsson, J. Postberg, D. Rhodes, and H.J. Lipps, Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo, Nat. Struct. Mol. Biol., Volume 12, 2005, Pages 847-854.

M.L. Zhang, X.J. Tong, X.H. Fu, B.O. Zhou, J. Wang, X.H. Liao, Q.J. Li, N. Shen, J. Ding, and J.Q. Zhou, Yeast telomerase subunit Est1p has guanine quadruplex-promoting activity that is required for telomere elongation, Nat. Struct. Mol. Biol., Volume 17, 2010, Pages 202-209.

V.A. Soldatenkov, A.A. Vetcher, T. Duka, and S. Ladame, First evidence of a functional interaction between DNA quadruplexes and poly(ADP-ribose) polymerase-1, ACS Chem. Biol., Volume 3, 2008, Pages 214-219.

V. Gonzalez, K. Guo, L. Hurley, and D. Sun, Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein, J. Biol. Chem., Volume 284, 2009, Pages 23622-23635.

J. Shklover, P. Weisman-Shomer, A. Yafe, and M. Fry, Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD-dependent gene expression, Nucleic Acids Res., Volume 38, 2010, Pages 2369-2377.

S. Bergqvist, M.A. Williams, R. O'Brien, and J.E. Ladbury, Heat capacity effects of water molecules and ions at a protein-DNA interface, J. Mol. Biol., Volume 336, 2004, Pages 829-842.

M.J. Law, K.M. Lower, H.P. Voon, J.R. Hughes, D. Garrick, V. Viprakasit, M. Mitson, M. De Gobbi, M. Marra, A. Morris, A. Abbott, S.P. Wilder, S. Taylor, G.M. Santos, J. Cross, H. Ayyub, S. Jones, J. Ragoussis, D. Rhodes, I. Dunham, D.R. Higgs, and R.J. Gibbons, ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner, Cell, Volume 143, 2010, Pages 367-378.

D.J. Uribe, K. Guo, Y.J. Shin, and D. Sun, Heterogeneous Nuclear Ribonucleoprotein K and Nucleolin as Transcriptional Activators of the Vascular Endothelial Growth Factor Promoter through Interaction with Secondary DNA Structures, Biochemistry, Volume 50, 2011, Pages 3796-3806.

K. Takahama, C. Sugimoto, S. Arai, R. Kurokawa, and T. Oyoshi, Loop Lengths of G-Quadruplex Structures Affect the G-Quadruplex DNA Binding Selectivity of the RGG Motif in Ewing's Sarcoma, Biochemistry, Volume 50, 2011, Pages 5369-5378.

H. Fernando, R. Rodriguez, and S. Balasubramanian, Selective recognition of a DNA G-quadruplex by an engineered antibody, Biochemistry, Volume 47, 2008, Pages 9365-9371.

Y.H. Wang, S. Amirhaeri, S. Kang, R.D. Wells, and J.D. Griffith, Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene, Science, Volume 265, 1994, Pages 669-671.

J.S. Godde, and A.P. Wolffe, Nucleosome assembly on CTG triplet repeats, J. Biol. Chem., Volume 271, 1996, Pages 15222-15229.

S. Pramanik, K. Nakamura, K. Usui, S. Nakano, S. Saxena, J. Matsui, D. Miyoshi, and N. Sugimoto, Thermodynamic stability of Hoogsteen and Watson-Crick base pairs in the presence of histone H3-mimicking peptide, Chem. Commun. (Camb.), Volume 47, 2011, Pages 2790-2792.

X.F. Zhang, J.F. Xiang, M.Y. Tian, Q.F. Yang, H.X. Sun, S. Yang, and Y.L. Tang, Formation of an intramolecular G-quadruplex of human telomere induced by poly(L-lysine) under salt-deficient conditions, J. Phys, Chem. B, Volume 113, 2009, Pages 7662-7667.

S. Nagatoishi, Y. Tanaka, and K. Tsumoto, Circular dichroism spectra demonstrate formation of the thrombin-binding DNA aptamer G-quadruplex under stabilizing-cation-deficient conditions, Biochem. Biophys. Res. Commun., Volume 352, 2007, Pages 812-817.

B. Pagano, L. Martino, A. Randazzo, and C. Giancola, Stability and binding properties of a modified thrombin binding aptamer, Biophys. J., Volume 94, 2008, Pages 562-569.

S. Nagatoishi, N. Isono, K. Tsumoto, and N. Sugimoto, Loop residues of thrombin-binding DNA aptamer impact G-quadruplex stability and thrombin binding, Biochimie, Volume 93, 2011, Pages 1231-1238.

A. Risitano, and K.R. Fox, Influence of loop size on the stability of intramolecular DNA quadruplexes, Nucleic Acids Res., 32, 2004, Pages 2598-2606.

P. Hazel, G.N. Parkinson, and S. Neidle, Predictive modelling of topology and loop variations in dimeric DNA quadruplex structures, Nucleic Acids Res., Volume 34, 2006, Pages 2117-2127.

S.M. Haider, G.N. Parkinson, and S. Neidle, Structure of a G-quadruplex-ligand complex, J. Mol. Biol., Volume 326, 2003, Pages 117-125.

J. Seenisamy, E.M. Rezler, T.J. Powell, D. Tye, V. Gokhale, C.S. Joshi, A. Siddiqui-Jain, and L.H. Hurley, The dynamic character of the G-quadruplex element in the c-MYC promoter and modification by TMPyP4, J. Am. Chem. Soc., Volume 126, 2004, Pages 8702-8709.

E. Hatzakis, K. Okamoto, and D. Yang, Thermodynamic stability and folding kinetics of the major G-quadruplex and its loop isomers formed in the nuclease hypersensitive element in the human c-Myc promoter: effect of loops and flanking segments on the stability of parallel-stranded intramolecular G-quadruplexes, Biochemistry, Volume 49, 2010, Pages 9152-9160.

K.J. Zanotti, P.E. Lackey, G.L. Evans, and M.R. Mihailescu, Thermodynamics of the fragile X mental retardation protein RGG box interactions with G quartet forming RNA, Biochemistry, Volume 45, 2006, Pages 8319-8330.

J.C. Darnell, K.B. Jensen, P. Jin, V. Brown, S.T. Warren, and R.B. Darnell, Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function, Cell, Volume 107, 2001, Pages 489-499.

A. Ramos, D. Hollingworth, and A. Pastore, G-quartet-dependent recognition between the FMRP RGG box and RNA, RNA, Volume 9, 2003, Pages 1198-1207.

B. Jayaram, and T. Jain, The role of water in protein-DNA recognition. Annu. Rev. Biophys. Biomol. Struct., Volume 33, 2004, Pages 343-361.

S. Curry, O. Kotik-Kogan, M.R. Conte, and P. Brick, Getting to the end of RNA: structural analysis of protein recognition of 5' and 3' termini, Biochim. Biophys. Acta, Volume 1789, 2009, Pages 653-666.

A. Niedzwiecka, J. Stepinski, E. Darzynkiewicz, N. Sonenberg, and R. Stolarski, Positive heat capacity change upon specific binding of translation initiation factor eIF4E to mRNA 5' cap, Biochemistry, Volume 41, 2002, Pages 12140-12148.

L. Jen-Jacobson, L.E. Engler, and L.A. Jacobson, Structural and thermodynamic strategies for site-specific DNA binding proteins, Structure, Volume 8, 2000, Pages 1015-1023.

S. Nagatoishi, N. Isono, K. Tsumoto, and N. Sugimoto, Hydration is Required in DNA G-Quadruplex-Protein Binding, ChemBioChem, 2011, in press, DOI: 10.1002/cbic.201100264.

J.R. Bothe, K. Lowenhaupt, and H.M. Al-Hashimi, Sequence-specific B-DNA flexibility modulates Z-DNA formation, J. Am. Chem. Soc., Volume 133, 2011, Pages 2016-2018.

E.N. Nikolova, E. Kim, A.A. Wise, P.J. O'Brien, I. Andricioaei, and H.M. Al-Hashimi, Transient Hoogsteen base pairs in canonical duplex DNA, Nature, Volume 470, 2011, Pages 498-502.

A. Roth, and R.R. Breaker, The structural and functional diversity of metabolite-binding riboswitches, Annu. Rev. Biochem., Volume 78, 2009, Pages 305-334.

D.H. Zhang, T. Fujimoto, S. Saxena, H.Q. Yu, D. Miyoshi, and N. Sugimoto, Monomorphic RNA G-quadruplex and polymorphic DNA G-quadruplex structures responding to cellular environmental factors, Biochemistry, Volume 49, 2010, Pages 4554-4563.

S. Saxena, D. Miyoshi, and N. Sugimoto, Sole and stable RNA duplexes of G-rich sequences located in the 5'-untranslated region of protooncogenes, Biochemistry, Volume 49, 2010, Pages 7190-7201.


  • There are currently no refbacks.

Please send any question about this web site to info@praiseworthyprize.com
Copyright © 2005-2024 Praise Worthy Prize