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Molecular Principles of the Spontaneous Mutagenesis in DNA

Ol’ha Brovarets`1,2 o.o.brovarets [at] imbg.org.ua
  1. Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Ukraine, Kyiv, Akademika Zabolotnoho street 150.
  2. Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine, Kyiv, Akademika Hlushkova avenue 2-h.
Abstract 

Reported results are crucial for understanding of the microstructural mechanisms of the spontaneous transitions and transversions, since they allow us to explain, from the one side, the origin of the mutagenic tautomers at the separation of the DNA strands before its replication and, from the other side, in what way occurs the adaptation of the incorrect purine·pyrimidine, purine·purine and pyrimidine·pyrimidine wobble pairs to the enzymatically competent sizes in the recognition pocket of the high-fidelity DNA-polymerase. 

Keywords 
spontaneous point mutagenesis
incorporation and replication errors
tautomerisation
pairs of nucleotide bases
enzymatically-competent conformation
hydrogen bond
quantum chemistry
References 
  1. Cooper, G.M. The Cell (2nd edition). A molecular approach. Boston University. Sunderland (MA): Sinauer Associates, 2000.
  2. Freese, E.B. On the molecular explanation of spontaneous and induced mutations. Brookhaven Symp. Biol., 1959, 12, 63-75.
  3. von Borstel, R.C. Origins of spontaneous base substitutions. Mutation Research, 1994, 307, 131-140.
  4. Friedberg, E.C., Walker, G.C., Siede, W., Wood, R.D., Schultz, R.A., & Ellenberger, T. DNA repair and mutagenesis. Washington D.C.: ASM Press, 2006.
  5. Drake, J.W., Charlesworth, B., Charlesworth, D., & Crow, J.F. Rates of spontaneous mutation. Genetics, 1998, 148, 1667–1686.
  6. Lee, H., Popodi, E., Tang, H., & Foster, P.L. Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by wholegenome sequencing. Proc. Natl. Acad. Sci. USA, 2012, 109, E2774-E2783.
  7. Lynch, M. Rate, molecular spectrum, and consequences of human mutation. Proc. Natl. Acad. Sci. USA, 2010, 107, 961-968.
  8. Fijalkowska, I.J., Schaaper, R.M., & Jonczyk, P. DNA replication fidelity in Escherichia coli: a multi-DNA polymerase affair. FEMS Microbiol. Rev., 2012, 36, 1105–1121.
  9. Watson, J. D., & Crick, F. H. C. The Structure of DNA. Cold Spring Harb. Symp. Quant. Biol., 1953, 18, 123-131.
  10. Topal, M.D., & Fresco, J.R. Complementary base pairing and the origin of substitution mutations. Nature, 1976, 263, 285-289.
  11. Nedderman, A.N., Stone, M.J., Lin, P.K.T., Brown, D.M., & Williams, D.H. Base pairing of cytosine analogues with adenine and guanine in oligonucleotide duplexes: evidence for exchange between Watson-Crick and wobble base pairs using 1H NMR spectroscopy.  J. Chem. Soc. Chem. Commun., 1991, 1357–1359.
  12. Nedderman, A.N., Stone, M.J., Williams, D.H., Lin, P.K.Y., & Brown DM. Molecular basis for methoxyamine-initiated mutagenesis: 1H nuclear magnetic resonance studies of oligonucleotide duplexes containing base-modified cytosine residues. J. Mol. Biol., 1993, 230, 1068-1076.
  13. Harris, V. H., Smith, C.L., Jonathan Cummins, W., Hamilton, A.L., Adams, H., Dickman, M., Hornby, D.P., & Williams, D.M. The effect of tautomeric constant on the specificity of nucleotide incorporation during DNA replication: support for the rare tautomer hypothesis of substitution mutagenesis. J. Mol. Biol., 2003, 326, 1389–1401.
  14. Bebenek, K., Pedersen, L.C., & Kunkel, T.A. Replication infidelity via a mismatch with Watson−Crick geometry. Proc. Natl. Acad. Sci. USA, 2011, 108, 1862−1867.
  15. Wang, W., Hellinga, H. W., & Beese, L. S. Structural evidence for the rare tautomer hypothesis of spontaneous mutagenesis. Proc. Natl. Acad. Sci. USA, 2011, 108, 17644−17648.
  16. Kimsey, I.J., Petzold, K., Sathyamoorthy, B., Stein, Z.W., & Al-Hashimi, H.M. Visualizing transient Watson-Crick-like mispairs in DNA and RNA duplexes. Nature, 2015, 519, 315-320.
  17. Danilov, V.I., Anisimov, V.M., Kurita, N., & Hovorun, D. MP2 and DFT studies of the DNA rare base pairs: the molecular mechanism of the spontaneous substitution mutations conditioned by tautomerism of bases. Chem. Phys. Lett., 2005, 412, 285-293.
  18. Fonseca Guerra, C., Bickelhaupt, F.M., Saha, S., & Wang, F. Adenine tautomers: relative stabilities, ionization energies, and mismatch with cytosine. J. Phys. Chem. A, 2006, 110, 4012-4020.
  19. Löwdin P.-O. Proton tunneling in DNA and its biological implications. Rev. Mod. Phys., 1963, 35, 724-732.
  20. Löwdin P.-O. Quantum genetics and the aperiodic solid: Some aspects on the biological problems of heredity, mutations, aging, and tumors in view of the quantum theory of the DNA molecule. In Löwdin, P.-O. (Ed.) Advances in Quantum Chemistry (1966, 2, pp. 213360). New York, USA, London, UK: Academic Press.
  21. Godbeer, A.D., Al-Khalili, J.S., & Stevenson, P.D. Modelling proton tunneling in the adenine-thymine base pair. Phys. Chem. Chem. Phys., 2015, 17, 13034-13044.
  22. Turaeva, N., & Brown-Kennerly, V. Marcus model of spontaneous point mutation in DNA. Chem. Phys., 2015, 461, 106-110.
  23. Padermshoke, A., Katsumoto, Y., Masaki, R., & Aida, M. Thermally induced double proton transfer in GG and wobble GT base pairs: A possible origin of the mutagenic guanine. Chem. Phys. Lett., 2008, 457, 232–236.
  24. Strazewski, P., & Tamm, C. Replication experiments with nucleotide base analogues. Ang. Chemie Int. Ed., 1990, 29, 36–57.
  25. Brown, T., Kennard, O., Kneale, G., & Rabinovich, D. High-resolution structure of a DNA helix containing mismatched base pairs. Nature, 1985, 315, 604-606.
  26. Kool E. T. Active site tightness and substrate fit in DNA replication. Annu. Rev. Biochem., 2002, 71, 191-219.
  27. Rossetti, G., Dans, P.D., Gomez-Pinto, I., Ivani, I., Gonzalez, C., & Orozco, M. The structural impact of DNA mismatches. Nucleic Acids Res., 2015, 43, 4309-4321.
  28. Aguilera, A., & Gómez-González, B. Genome instability: a mechanistic view of its causes and consequences. Nat. Rev. Genet., 2008, 9, 204-217.
  29. Rudd, S.G., Valerie N.C.K., & Helleday, T. Pathways controlling dNTP pools to maintain genome stability. DNA Repair, 2016, 44, 193–204.
  30. Jordheim, L.P., Durantel, D., Zoulim, F., & Dumontet, C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat. Rev. Drug Discov., 2013, 12, 447-464.
  31. Galmarini, C.M., Mackey, J.R., & Dumontet, C. Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol., 2002, 3, 415–424.
  32. Del Grosso, E., Dallaire, A.-M., Vallée-Bélisle, A., & Ricci, F. Enzyme-operated DNA-based nanodevices. Nano Lett., 2015, 15, 8407–8411.
  33. Liedl, T., Sobey, T.L., & Simmel, F.C. DNA-based nanodevices. Nanotoday, 2007, 2, 36-41.
  34. Piccolino, M. Biological machines: from mills to molecules. Nat. Rev. Mol. Cell Biol., 2000, 1, 149-153.
  35. Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., & Cheeseman, J.R., … Pople, J.A. (2010). GAUSSIAN 09 (Revision B.01). Wallingford CT: Gaussian Inc.
  36. Tirado-Rives, J., & Jorgensen, W.L. Performance of B3LYP Density Functional Methods for a large set of organic molecules. J. Chem. Theory Comput., 2008, 4, 297–306.
  37. Wiberg, K.B. Basis set effects on calculated geometries: 6-311++G** vs. aug-cc-pVDZ. J. Comput. Chem., 2004, 25, 1342-1346.
  38. Parr, R.G., & Yang, W. Density-functional theory of atoms and molecules. Oxford: Oxford University Press, 1989.
  39. Hratchian, H.P., & Schlegel, H.B. Finding minima, transition states, and following reaction pathways on ab initio potential energy surfaces. In Dykstra, C.E., Frenking, G., Kim, K.S., & Scuseria, G. (Eds.), Theory and applications of computational chemistry: The first 40 years (pp. 195-249). Amsterdam: Elsevier, 2005.
  40. Bader, R.F.W. Atoms in molecules: A quantum theory. Oxford: Oxford University Press, 1990.
  41. Atkins, P.W. Physical chemistry. Oxford: Oxford University Press, 1998.
  42. Brovarets', O.O. Microstructural mechanisms of the origin of the spontaneous point mutations. DrSci Thesis: Taras Shevchenko National University of Kyiv, Kyiv, Ukraine, 2015.
  43. Brovarets’, O.O., & Hovorun, D.M. Can tautomerisation of the A∙T Watson-Crick base pair via double proton transfer provoke point mutations during DNA replication? A comprehensive QM and QTAIM analysis. J. Biomol. Struct. & Dynam., 2014, 32, 127-154.
  44. Brovarets’, O.O., & Hovorun, D.M. Why the tautomerization of the G·C Watson–Crick base pair via the DPT does not cause point mutations during DNA replication? QM and QTAIM comprehensive analysis. J. Biomol. Struct. & Dynam., 2014, 32, 1474-1499.
  45. Brovarets' O.O., Hovorun D.M. Proton tunneling in the A∙T Watson-Crick DNA base pair: myth or reality? J. Biomol. Struct. & Dynam., 2015, 33, 12, 2716-2720.
  46. Brovarets', O.O., Zhurakivsky, R.O., & Hovorun, D.M. DPT tautomerisation of the wobble guanine·thymine DNA base mispair is not mutagenic: QM and QTAIM arguments. J. Biomol. Struct. & Dynam., 2015, 33, 674-689.
  47. Brovarets’ O.O., Yurenko Ye.P., Dubey I.Ya., & Hovorun D.M. Can DNA-binding proteins of replisome tautomerize nucleotide bases? Ab initio model study. J. Biomol. Struct. & Dynam., 2012, 29, 1101–1109.  
  48. Brovarets' O.O., Zhurakivsky R.O., & Hovorun D.M. Is the DPT tautomerisation of the long A·G Watson-Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question. J. Comput. Chem., 2014, 35, 451-466.
  49. Brovarets' O.O., & Hovorun D.M. The physicochemical essence of the purine·pyrimidine transition mismatches with Watson-Crick geometry in DNA: A·C* versa A*·C. A QM and QTAIM atomistic understanding. J. Biomol. Struct. & Dynam., 2015, 33, 28-55.
  50. Brovarets' O.O., & Hovorun D.M. The nature of the transition mismatches with Watson-Crick architecture: the G*·T or G·T* DNA base mispair or both? A QM/QTAIM perspective for the biological problem. J. Biomol. Struct. & Dynam., 2015, 33, 925-945.
  51. Brovarets' O.O., & Hovorun D.M. Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches. J. Comput. Chem., 2013, 34, 2577-2590.
  52. Brovarets' O.O., & Hovorun D.M. Does the G·G*syn DNA mismatch containing canonical and rare tautomers of the guanine tautomerise through the DPT? A QM/QTAIM microstructural study. Mol. Phys., 2014, 112, 3033-3046.
  53. Brovarets' O.O., Zhurakivsky R.O., & Hovorun D.M. Does the tautomeric status of the adenine bases change upon the dissociation of the А*·Аsyn Topal-Fresco DNA mismatch? A combined QM and QTAIM atomistic insight. Phys. Chem. Chem. Phys., 2014, 16, 3715-3725.
  54. Brovarets' O.O., & Hovorun D.M. DPT tautomerisation of the G·Asyn and A*·G*syn DNA mismatches: a QM/QTAIM combined atomistic investigation. Phys. Chem. Chem. Phys., 2014, 16, 9074-9085.
  55. Brovarets' O.O., Zhurakivsky R.O., & Hovorun D.M. Structural, energetic and tautomeric properties of the T·T*/T*·T DNA mismatch involving mutagenic tautomer of thymine: a QM and QTAIM insight. Chem. Phys. Lett., 2014, 592, 247-255.
  56. Brovarets' O.O., & Hovorun D.M. Atomistic nature of the DPT tautomerisation of the biologically important C·C* DNA base mispair containing amino and imino tautomers of cytosine: а QM and QTAIM approach. Phys. Chem. Chem. Phys., 2013, 15, 20091-20104. 
  57. Brovarets' O.O., & Hovorun D.M. DPT tautomerization of the long A·A* Watson-Crick base pair formed by the amino and imino tautomers of adenine: combined QM and QTAIM investigation. J. Mol. Model., 2013, 19, 4223-4237.
  58. Brovarets' O.O., & Hovorun D.M. How does the long G·G* Watson-Crick DNA base mispair comprising keto and enol tautomers of the guanine tautomerise? The results of а QM/QTAIM investigation. Phys. Chem. Chem. Phys., 2014, 16, 15886-15899.
  59. Brovarets' O.O., & Hovorun D.M. New structural hypostases of the A·T and G·C Watson-Crick DNA base pairs caused by their mutagenic tautomerisation in a wobble manner: a QM/QTAIM prediction. RSС Adv., 2015, 5, 99594-99605.
  60. Brovarets’, O.O., & Hovorun, D.M. Physicochemical mechanism of the wobble DNA base pairs Gua·Thy and Ade·Cyt transition into the mismatched base pairs Gua*·Thy and Ade·Cyt* formed by the mutagenic tautomers. Ukr. Bioorg. Acta, 2009, 8, 12-18.
  61. Brovarets' O.O., & Hovorun D.M. Tautomeric transition between wobble А·С DNA base mispair and WatsonCrick-like A·C* mismatch: miscrostructural mechanism and biological significance. Phys. Chem. Chem. Phys., 2015, 17, 15103-15110.
  62. Brovarets' O.O., & Hovorun D.M. How many tautomerisation pathways connect Watson-Crick-like G*·T DNA base mispair and wobble mismatches? J. Biomol. Struct. & Dynam., 2015, 33, 2297-2315.
  63. Brovarets’, O.O., & Hovorun, D. M. Wobble↔WatsonCrick tautomeric transitions in the homo-purine DNA mismatches: a key to the intimate mechanisms of the spontaneous transversions. J. Biomol. Struct. & Dynam., 2015, 33, 2710-2715.
  64. Brovarets’, O.O., & Hovorun, D.M. Novel physicochemical mechanism of the mutagenic tautomerisation of the Watson–Crick-like A·G and C·T DNA base mispairs: a quantum-chemical picture. RSC Adv., 2015, 5, 66318-66333.
  65. Brovarets', O.O., & Hovorun, D.M. A novel conception for spontaneous transversions caused by homopyrimidine DNA mismatches: a QM/QTAIM highlight. Phys. Chem. Chem. Phys., 2015, 17, 21381-21388.
  66. Brovarets’, O.O., Pérez-Sánchez, H.E., & Hovorun, D.M. Structural grounds for the 2-aminopurine mutagenicity: A novel insight into the old problem of the replication errors. RSС Adv., 2016, 6, 99546-99557.
  67. Brovarets’, O.O., & Pérez-Sánchez, H.E. Whether 2aminopurine induces incorporation errors at the DNA replication? A quantum-mechanical answer on the actual biological issue. J. Biomol. Struct. & Dynam., 2016, DOI: 10.1080/07391102.2016.1253504.
  68. Brovarets’, O.O., & Pérez-Sánchez, H.E. Whether the amino-imino tautomerism of 2-aminopurine is involved into its mutagenicity? Results of a thorough QM investigation. RSС Adv., 2016, DOI: 10.1039/C6RA24277D.
  69. Huang, M.M., Arnheim, N., & Goodman, M.F. Extension of base mispairs by Taq DNA polymerase: implications for single nucleotide discrimination in PCR. Nucleic Acids Res., 1992, 20, 4567-4573.