DNA Damage Emanating From a Neutral Purine Radical Reveals the Sequence Dependent Convergence of the Direct and Indirect Effects of γ-Radiolysis

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2017 Dec 1

PMID 29190086

Citations 14

Authors

Liwei Zheng

Marc M Greenberg

Affiliations

Soon will be listed here.

Abstract

Nucleobase radicals are the major intermediates generated by the direct (e.g., dA) and indirect (e.g., dA•) effects of γ-radiolysis. dA• was independently generated in DNA for the first time. The dA/dA• equilibrium, and consequently the reactivity in DNA, is significantly shifted toward the radical cation by a flanking dA. Tandem lesions emanating from dA• are the major products when the reactive intermediate is flanked by a 5'-dGT. In contrast, when dA• is flanked by dA, the increased dA pK results in DNA damage arising from hole transfer. This is the first demonstration that sequence effects lead to the intersection of the direct and indirect effects of ionizing radiation.

Citing Articles

Deprotonation of 8-Oxo-7,8-dihydroadenine Radical Cation in Free and Encumbered Context: A Theoretical Study.

Wang Y, Ma L, Wei S ACS Omega. 2025; 9(51):50730-50741.

PMID: 39741838 PMC: 11683639. DOI: 10.1021/acsomega.4c08956.

CO protects cells from iron-Fenton oxidative DNA damage in and humans.

Fleming A, Dingman J, Burrows C Proc Natl Acad Sci U S A. 2024; 121(49):e2419175121.

PMID: 39602264 PMC: 11626140. DOI: 10.1073/pnas.2419175121.

Why the ROS matters: One-electron oxidants focus DNA damage and repair on G-quadruplexes for gene regulation.

Fleming A, Burrows C DNA Repair (Amst). 2024; 145:103789.

PMID: 39580976 PMC: 11757056. DOI: 10.1016/j.dnarep.2024.103789.

CO protects cells from iron-Fenton oxidative DNA damage in E. coli and humans.

Fleming A, Dingman J, Burrows C bioRxiv. 2024; .

PMID: 39253463 PMC: 11383276. DOI: 10.1101/2024.08.26.609766.

Nitrogen-Centered Radicals Derived from Azidonucleosides.

Reyes Y, Adhikary A, Wnuk S Molecules. 2024; 29(10).

PMID: 38792171 PMC: 11124349. DOI: 10.3390/molecules29102310.

References

Renaud N, Berlin Y, Lewis F, Ratner M . Between superexchange and hopping: an intermediate charge-transfer mechanism in poly(A)-poly(T) DNA hairpins. J Am Chem Soc. 2013; 135(10):3953-63. DOI: 10.1021/ja3113998. View

Hong I, Carter K, Greenberg M . Evidence for glycosidic bond rotation in a nucleobase peroxyl radical and its effect on tandem lesion formation. J Org Chem. 2004; 69(21):6974-8. DOI: 10.1021/jo0492158. View

Kobayashi K . Evidence of formation of adenine dimer cation radical in DNA: the importance of adenine base stacking. J Phys Chem B. 2010; 114(16):5600-4. DOI: 10.1021/jp100589w. View

Schuster G . Long-range charge transfer in DNA: transient structural distortions control the distance dependence. Acc Chem Res. 2000; 33(4):253-60. DOI: 10.1021/ar980059z. View

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(6844):318-20. DOI: 10.1038/35085542. View

Jones G, Boswell T, Lee J, Milligan J, Ward J, Weinfeld M . A comparison of DNA damages produced under conditions of direct and indirect action of radiation. Int J Radiat Biol. 1994; 66(5):441-5. DOI: 10.1080/09553009414551431. View

KRISCH R, Flick M, Trumbore C . Radiation chemical mechanisms of single- and double-strand break formation in irradiated SV40 DNA. Radiat Res. 1991; 126(2):251-9. View

Sharma K, Swarts S, Bernhard W . Mechanisms of direct radiation damage to DNA: the effect of base sequence on base end products. J Phys Chem B. 2011; 115(16):4843-55. PMC: 3085925. DOI: 10.1021/jp200902h. View

Steenken S . Electron transfer in DNA? Competition by ultra-fast proton transfer?. Biol Chem. 1998; 378(11):1293-7. View

10.

Genereux J, Barton J . Mechanisms for DNA charge transport. Chem Rev. 2010; 110(3):1642-62. PMC: 2879062. DOI: 10.1021/cr900228f. View

11.

Hong I, Carter K, Sato K, Greenberg M . Characterization and mechanism of formation of tandem lesions in DNA by a nucleobase peroxyl radical. J Am Chem Soc. 2007; 129(13):4089-98. DOI: 10.1021/ja0692276. View

12.

Adhikary A, Kumar A, Khanduri D, Sevilla M . Effect of base stacking on the acid-base properties of the adenine cation radical [A*+] in solution: ESR and DFT studies. J Am Chem Soc. 2008; 130(31):10282-92. PMC: 4590776. DOI: 10.1021/ja802122s. View

13.

Galm U, Hager M, Van Lanen S, Ju J, Thorson J, Shen B . Antitumor antibiotics: bleomycin, enediynes, and mitomycin. Chem Rev. 2005; 105(2):739-58. DOI: 10.1021/cr030117g. View

14.

Carter K, Greenberg M . Tandem lesions are the major products resulting from a pyrimidine nucleobase radical. J Am Chem Soc. 2003; 125(44):13376-8. DOI: 10.1021/ja036629u. View

15.

ONeill P, Wardman P . Radiation chemistry comes before radiation biology. Int J Radiat Biol. 2009; 85(1):9-25. DOI: 10.1080/09553000802640401. View

16.

Kawai K, Takada T, Tojo S, Majima T . Kinetics of weak distance-dependent hole transfer in DNA by adenine-hopping mechanism. J Am Chem Soc. 2003; 125(23):6842-3. DOI: 10.1021/ja034953j. View

17.

Hall D, Holmlin R, Barton J . Oxidative DNA damage through long-range electron transfer. Nature. 1996; 382(6593):731-5. DOI: 10.1038/382731a0. View

18.

Patrzyc H, Dawidzik J, Budzinski E, Freund H, Wilton J, Box H . Covalently linked tandem lesions in DNA. Radiat Res. 2012; 178(6):538-42. PMC: 3557944. DOI: 10.1667/RR2915.1. View

19.

Tchou J, Kasai H, Shibutani S, Chung M, Laval J, Grollman A . 8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci U S A. 1991; 88(11):4690-4. PMC: 51731. DOI: 10.1073/pnas.88.11.4690. View

20.

Giese B . Long-distance electron transfer through DNA. Annu Rev Biochem. 2002; 71:51-70. DOI: 10.1146/annurev.biochem.71.083101.134037. View