To the understanding of the mechanism of formation of point mutations in DNA

Kryachko, ES, Volkov, SN
Dopov. Nac. akad. nauk Ukr. 2018, 7:103-112
Section: Biophysics
Language: Ukrainian

A mechanism for the point mutations formation in DNA is proposed, which takes into account the fluctuating appearance of the complementary pairs preopened by water molecules in the double helix. In the framework of the density functional method, possible transitions of protons in the preopened A · T pair are analyzed, and their structures and energies are calculated. It has been shown that the formation of preopened base pairs in the DNA catalyzes the stability of the non-regular forms of nucleic bases, which can serve as the source of a point mutation. The estimated probability of such mutation occurrence in DNA (10−10—10−11) explains the known experimental data.

Keywords: DNA, nucleic bases, point mutation, quantum chemistry, tautomers
  1. Watson, J. D. & Crick, F. H. C. (1953). The structure of DNA. Cold Spring Harb. Symp. Quant. Biol., 18, pp. 123-131. doi: 10.1101/SQB.1953.018.01.020
  2. Löwdin, P.-O. (1963). Proton tunneling in DNA and its biological implications. Rev. Mod. Phys., 35, pp. 724-732. doi:
  3. Danilov, V. I., Kvencel', G. F. (1971). Electronic representations in the theory of point mutations. Kiev: Naukova Dumka (in Russian).
  4. Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A. & Ellenberger, T. (2006). DNA repair and mutagenesis. Washington: ASM Press.
  5. Florián, J., Hrouda, V. & Hobza, P. (1994). Proton transfer in the adenine-thymine base pair. J. Am. Chem. Soc., 116, pp. 1457-1460. doi:
  6. Gorb, L., Podolyan, Y., Dziekonski, P., Sokalski, J. & Leszczynski, W.A. (2004). Double-proton transfer in adenine-thymine and guanine-cytosine base pairs. A Post-Hartree-Fock ab Initio Study. J. Am. Chem. Soc., 126, pp. 10119-10129. doi:
  7. Brovarets', O. O., Hovorun, D. M. (2015). New structural hypostasis 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. RSS Adv., 5, pp. 99594-99605. doi:
  8. Poltev, V. I., Kosevich, M. V., Shchelkovskii, V. S., Pashinskaya, V. A., Gonzalez, E., Teplukhin, A. V., & Malenkov, G. G. (1995). Mechanism of nucleic base tautomerization upon dehydration. Molekulyar. biologiya, 29, pp. 220-223 (in Russian).
  9. Kryachko, E. S. & Volkov, S. N. (2001). Preopening of the DNA base pairs. Int. J. Quantum Chem., 82, pp. 193-204. doi:
  10. Frank-Kamenetskii, M. D. (1983). Fluctuation mobility of DNA. Molekulyar. biologiya, 17, pp. 639-652 (in Russian).
  11. Volkov, S. N. (1995). Preopened state of DNA double helix. Molekulyar. biologiya, 29, pp. 1086-1094 (in Russian).
  12. Frank-Kamenetskii, M. D. & Prakash, S. (2014). Fluctuations in the DNA double helix: A critical review. Phys. Life. Rev., 11, No. 2, pp. 153-170. doi:
  13. Giudice, E., Várnai, P. & Lavery, R. (2003). Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations. Nucl. Acids Res., 31, pp. 1434-1443. doi:
  14. Mandal, C., Kallenbach, N. R. & Englander S. W. (1979). Base-pair opening and closing reactions in the double helix: A stopped-flow hydrogen exchange study in poly(rA) • poly(rU). J. Mol. Biol., 135, pp. 391-411. doi:
  15. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery Jr., J. A., Peralta, J. E., Ogliaro, F., Bearpark, M., Heyd, J. J., Brothers, E., Kudin, K. N., Staroverov, V. N., Keith, T., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J. C., Iyengar, S. S., Tomasi, J., Cossi, M., Rega, N., Millam, J. M., Klene, M., Knox, J. E., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Martin, R. L., Morokuma, K., Zakrzewski, V. G., Voth, G. A., Salvador, P., Dannenberg, J. J., Dapprich, S., Daniels, A. D., Farkas, O., Foresman, J. B., Ortiz, J. V., Cioslowski, J., Fox, D. J. (2010). Gaussian 09, Revision C.01. Wallingford CT: Gaussian, Inc.