Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Attacking mechanism of H and OH radicals to DNA base pair: DFT calculations in water

Genetic information recorded in DNA can be damaged indirectly by radiation. Such interaction of radiation to the water molecules in living organs produces the ionization of water molecules, leading to highly reactive H and OH radicals. Because these radicals react with organic cellular components, especially DNA and lipids, DNA is damaged in its structure and electronic properties. In the solvated medium, OH radicals reach active sites of the DNA molecule and remove a hydrogen ion from the sugar moiety or nucleobase of DNA. As a consequence, the native double-helical structure of DNA is altered leading to errors in the genetic information stored in DNA (Cooke et al., 2003). It is thus important to understand the damage in DNA induced by the attack of radicals for revealing the indirect effect of radiation on DNA.

In order to elucidate the effect, we have investigated the attacking mechanism of OH radical to the G-C and A-T base pairs, by the density functional theory (DFT) calculations (Shimizu, et al., 2015). The effect of solvation on the mechanism was also revealed by performing the same DFT calculations in water approximated by a continuum solvation model. The results elucidated that the hydrogen atom of NH2 group of G or A base is abstracted by the OH radical. The solvation around the base pairs stabilizes the dehydrogenated structures significantly, resulting in the acceleration of the attacking reaction by OH radical to the base pairs in the water. In the present study, we searched for the transition states of the attacking reactions of H and OH radicals to the DNA base pairs in the water, using the DFT calculations. The results elucidate that H radical affects significantly G-C base pair to cause the tautomeric reaction into G*-C* form, while OH radical can cause tautomeric reaction in A-T base pair, as shown below. The details of the results simulated will be presented at the meeting.


Figure Change in structure during tautomeric reaction for (a) G-C+H-radical and (b) A-T+OH-radical

M. S. Cooke, et al., FASEB J., 2003, 17, 1195-1214.

E. Shimizu, et al., J. of Biomolecular Structure and Dynamics, 2015, 33, 158-166.

This research has been supported by the JSPS Grant-in-Aid for Challenging Exploratory Research [grant number 22650061].

Naoko Okutsu1
Eisuke Shimizu1
Victor I. Danilov2
Sergiy Shulga2
Noriyuki Kurita1*

1Toyohashi University of Technology
Aichi, 441-8580, Japan
2National Academy of Sciences of Ukraine
Kyiv, Ukraine

*Tel. & Fax.: +81-532-44-6875