Abstract
This study describes the influence of the phosphorothioate internucleotide bond on the deoxyribonucleic acid (DNA) oxidation process. The interaction of an ultraviolet radiation (UVA) with a targeted double-stranded (ds) oligonucleotide, in which one strand contains an antraquinone (AQ) moiety on the 5’-end, may lead to a hole migration process through the double helix. In the end, the migration of theformed radical cation terminates in a suitable place. Usually, this is a guanine-rich sequence. In another experiment, phosphorothioate internucleotide bonds were detected in the bacterial genome as a natural modification. In this study, a polyacrylamide gel electrophoresis (PAGE) autoradiogram analysis of irradiated ds-DNA showed that the oxidation reaction was not inhibited by an isolated guanine. Instead, irrespective of the absence or presence of a phosphorothioate bond, the termination of the ds-DNA oxidation process was predominantly observed on the thymine moieties. Based on the obtained results, it can be concluded that in the discussed case, a hole migration by a hopping mechanism is in competition with an oxidation reaction with a superoxide radical anion. Alternatively, the radical cation migration process is sequence-dependent due to its different ionization potentials. Therefore, the presence of a phosphorothioate internucleotide bond did not change the stability of ds-DNA under UVA irradiation conditions.
Graphical Abstract
References
[1] Watson, J.D., Baker T.A., Bell S.P., Gann A., Levine M., Losick R., Molecular biology of the gene, 5th ed., Cold Spring Harbor Laboratory Press, San Francisco, 2004. Search in Google Scholar
[2] Panasci, L.C., Alaoui-Jamali M.A. (Eds.), DNA repair in cancer therapy, Human Press, 2004. 10.1007/978-1-59259-735-2Search in Google Scholar
[3] Cook, M.S., Evans M.D., Dizdaroglu M., Lunec J., Oxidative DNA damage: mechanisms, mutation and disease, FASEB J., 2003, 17, 1195-1214. 10.1096/fj.02-0752revSearch in Google Scholar PubMed
[4] Burrows, C., Muller J.G., Oxidative nucleobase modifications leading to strand scission, Chem. Rev., 1998, 98, 1109-1152. 10.1021/cr960421sSearch in Google Scholar PubMed
[5] Eberhardt, M.K., Reactive oxygen metabolites: chemistry and medical consequences, Boca Raton: CRC Press, 2001. 10.1201/9781420041521Search in Google Scholar
[6] Misiszek, R., Crean C., Joffe A., Geacintov N.E., Shafirovich V., Oxidative DNA damage associated with combination of guanine and superoxide radicals and repair mechanisms via radical trapping, J. Biol. Chem., 2004, 297, 32106-32115. 10.1074/jbc.M313904200Search in Google Scholar PubMed
[7] Wagneknecht, H-A. (Eds.), Charge transfer in DNA: from mechanism to application, Wiley-VCH Verlag GmbH & Co. KgaA, 2005. Search in Google Scholar
[8] Rokhlenko Y., Geacintiv N.E., Shafirovich N., Lifetimes and reaction pathway of guanine radical cations and neutral guanine radicals in an oligonucleotide in aqueous solutions, J. Am. Chem. Soc., 2012, 134, 4955-4962. 10.1021/ja212186wSearch in Google Scholar PubMed PubMed Central
[9] Rokhlenko, Y., Cadet J., Geacintov N.E., Shafirovich V., Mechanistic aspects of hydration of guanine radical cation in DNA, J. Am. Chem. Soc., 2014, 136, 5956-5962. 10.1021/ja412471uSearch in Google Scholar PubMed PubMed Central
[10] Genereux, J.C., Barton J.K., Mechanisms for DNA charge transport, Chem. Rev., 2010, 110, 1642-1662. 10.1021/cr900228fSearch in Google Scholar PubMed PubMed Central
[11] Chworos, A., Coppel, Y., Dubey, I., Pratviel, G., Meunier B., Guanine oxidation: NMR characterization of a dehydro-guanidinohydantoin residue generated by a 2e-oxidation of d(GpT), J. Am. Chem. Soc., 2001, 123, 5867-5877. 10.1021/ja003945pSearch in Google Scholar PubMed
[12] Chworos, A., Seguy, Ch., Pratviel, G., Meunier B., Characterization of the dehydro-guanidinohydantoin oxidation product of guanine in a dinucleotide, Chem. Res. Toxicol., 2002, 15, 1643-1651. 10.1021/tx0200717Search in Google Scholar PubMed
[13] Karwowski, B., Dupeyrat, F., Bardet, M., Ravanat, J-L., Krajewski, P., Cadet J., Nuclear magnetic resonance studies of the 4R and 4S diastereomers of spiroiminodihydantoin 2′-deoxyribonucleosides: absolute configuration and conformational features, Chem. Res. Toxicol., 2006, 19, 1357-1365. 10.1021/tx060088fSearch in Google Scholar PubMed
[14] McCullough, A.K., Dodson, M.L., Lloyd R.S., Initiation of base excision repair: glycosylase mechanisms and structures, Ann. Rev. Biochem., 1999, 68, 255-285. 10.1146/annurev.biochem.68.1.255Search in Google Scholar PubMed
[15] Sancar, A., Lindsey-Boltz, L.A., Unsal-Kacmaz, K., Linn S., Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints, Ann. Rev. Biochem., 2004, 73, 39-85. 10.1146/annurev.biochem.73.011303.073723Search in Google Scholar PubMed
[16] Limon-Pacheco, J., Gonsebatt M.E., The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress, Mutat Res., 2009, 31, 137-147. 10.1016/j.mrgentox.2008.09.015Search in Google Scholar PubMed
[17] Wang, L., Chen, S., Xu, T., Taghizadeh, K., Wishnok, J.S., Zhou, X., et al., Phosphorothioation of DNA in bacteria by dnd genes, Nat. Chem. Biol., 2007, 3, 709–710. 10.1038/nchembio.2007.39Search in Google Scholar PubMed
[18] Kanvah, S., Schuster G.B., Oxidative damage to DNA: inhibition of guanine damage, Pure Appl. Chem., 2006, 78, 2297-2304. 10.1351/pac200678122297Search in Google Scholar
[19] Adhikary, A., Kumar, A., Palmer, B.J., Todd, A.D., Sevilla M.D., Formation of S–Cl phosphorothioate adduct radicals in dsDNA S-oligomers: hole transfer to guanine vs disulfide anion radical formation, J. Am. Chem. Soc., 2013, 135, 12827-12838. 10.1021/ja406121xSearch in Google Scholar PubMed PubMed Central
[20] Gasper, M.S., Shuster G.B., Intramolecular photoinduced electron transfer to anthraquinones linked to duplex DNA: the effect of gaps and traps on long-range radical cation migration, J. Am. Chem. Soc., 1997, 119, 12762-12771. 10.1021/ja972496zSearch in Google Scholar
[21] Karwowski, B., The influence of the terminal phosphorothioate diester bond on the DNA oxidation process. An experimental and theoretical approach, Molecules, 2015, 20, 12400-12411. 10.3390/molecules200712400Search in Google Scholar PubMed PubMed Central
[22] Breslin, D.T., Schuster G.B., Anthraquinone photonucleases: mechanisms for GG-selective and nonselective cleavage of double-stranded DNA, J. Am. Chem., Soc., 1996, 118, 2311-2319. 10.1021/ja953714wSearch in Google Scholar
[23] Quantity One 1-D analysis software, version 4.6.6., Bio-Rad Laboratories, CA, USA, 2000. Search in Google Scholar
[24] Brinboim H.C., Kanabus-Kaminska M., The production of DNA strand brakes in human leukocytes by superoxide anion my involve a metabolic process, Proc. Natl. Acad. Sci. USA, 1985, 82, 6820-6824. 10.1073/pnas.82.20.6820Search in Google Scholar PubMed PubMed Central
[25] Barnett, N.R., Cleceland, Ch.L., Landman, U., Boone, E., Kanvah, S., Schuster G.B., Effect of base sequence and hydration on the electronic and hole transport properties of duplex DNA: theory and experiment, J. Phys. Chem. A., 2003, 107, 3525-3537. 10.1021/jp022211rSearch in Google Scholar
[26] Sinha, N.D., Jung, K.E., Analysis and purification of synthetic nucleic acids using HPLC, Curr. Protoc. Nucleic Acid Chem., 2015, 61:10.5.1-10.5.39. 10.1002/0471142700.nc1005s61Search in Google Scholar PubMed
[27] Kanvah, S., Schuster G.B., One-electron oxidation of DNA: thymine versus guanine reactivity, Org. Biomol. Chem., 2010, 8, 1340-1343. 10.1039/b922881kSearch in Google Scholar PubMed
[28] Meggers, E., Michel-Beyerle, M.E., Giese B., Sequence dependent long range hole transport in DNA, J. Am. Chem. Soc., 1998, 120, 12950-12955. 10.1021/ja983092pSearch in Google Scholar
[29] Lewis, F.D., Zuo, X., Hayes R.T., Wasilewski M.R., Dynamics and inter- and intra-strand hole transport in DNA hairpins, J. Am. Chem. Soc., 2002, 124, 4568-4569. 10.1021/ja0177859Search in Google Scholar PubMed
[30] Joseph, J., Schuster G.B., Emergent functionality of nucleobase radical cations in duplex DNA: prediction of reactivity using qualitative potential energy landscapes, J. Am. Chem. Soc., 2006, 128, 6070-6074. 10.1021/ja060655lSearch in Google Scholar PubMed
[31] Ghosh. A., Joy, A., Schuster, G.B., Douki, T., Cadet J., Selectiveone-electronoxidation of duplex DNA oligomers: reaction at thymines, Org. Biomol. Chem., 2008, 6, 916-928. 10.1039/b717437cSearch in Google Scholar PubMed
[32] Liu, Ch-S., Hernandez, R., Schuster G.B., Mechanism for radical cation transport in duplex DNA oligonucleotides, J. Am. Chem. Soc., 2004, 126, 2877-2884. 10.1021/ja0378254Search in Google Scholar PubMed
[33] Senthilkumar K., Grozema F.C., Guerra C.F., Bickelhaupt F.M., Siebbeles L.D.A., Mapping the sites for selective oxidation of guanines in DNA, J. Am. Chem. Soc., 2003, 125, 13658-13659. 10.1021/ja037027dSearch in Google Scholar PubMed
[34] Giese, B., Amaudrut, J., Kohler, A., Spormann, M., Wessely S., Direct observation of hole transfer through DNA by hopping between adenine bases and by tunnelling, Nature, 2001, 412, 318-320. 10.1038/35085542Search in Google Scholar PubMed
[35] Schuster G.B., Landman U., The mechanism of long-distance radical cation transport in duplex DNA: ion-gated hopping of polaron-like distortions, Top Curr. Chem., 2004, 236, 139-161. 10.1007/b94414Search in Google Scholar
[36] Hong S., Greenberg M.M., Efficient DNA interstrand cross-link formation from a nucleotide radical, J. Am. Chem. Soc., 2005, 127, 3692-3693. 10.1021/ja042434qSearch in Google Scholar PubMed
[37] Karwowski, B. The influence of phosphorothioate on charge migration in double and single stranded DNA. The theoretical approach, Phys. Chem. Chem. Phys., 2015, 17, 21507-21516. 10.1039/C5CP01382HSearch in Google Scholar
[38] Xie, X., Liang, J., Pu, T., Xu, F., Yao, F., Yang, Y., et al., Phosphorothioate DNA as an antioxidant in bacteria, Nuc. Acid. Res., 2012, 40, 9115-9124. 10.1093/nar/gks650Search in Google Scholar PubMed PubMed Central
[39] Wu, L., White, D.E., Ye, C., Vogt, F.G., Terfloth, G.J., Matsuhashi H., Desulfurization of phosphorothioate oligonucleotides via the sulfur-by-oxygen replacement induced by the hydroxyl radical during negative electrospray ionization mass spectrometry, J. Mass. Spectrom., 2012, 47, 836-844. 10.1002/jms.3022Search in Google Scholar PubMed
© 2015 Boleslaw T. Karwowski
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