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Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Review Article

Endogenous Repair System of Oxidative Damage of DNA

Author(s): Anmol Sharma, Pawan Gupta and Pranav Kumar Prabhakar*

Volume 13, Issue 2, 2019

Page: [110 - 119] Pages: 10

DOI: 10.2174/2212796813666190221152908

Price: $65


DNA is one of the most important biomolecules of living cells which carries genetic information from generation to generation. Many endogenous and exogenous agents may disrupt the structure of DNA. Change in the cellular genome can lead to errors in replication, transcription and in protein synthesis. DNA damage occurs naturally or result from a metabolic and hydrolytic process which release some very active chemical entities like free radicals, Reactive Oxygen Species (ROS), Reactive Nitrogen Intermediate (RNI), Reactive Carbonyl Species (RCS), lipid peroxidation products and alkylating agents. Superoxide radical, hydroxyl radical and hydrogen peroxide cause a significant threat to cellular integrity by damaging the DNA, lipids, proteins and other biomolecules. Oxidative stress may be explained as a disturbance in the number of free radicals and our system’s ability to neutralize these free radicals. Imbalances in the normal redox potential can also lead to toxic effects via the generation of peroxides. Oxidation of DNA bases leads to the base damage, nick in the strand and break in the strand either single or double strand. Oxidative stress can also cause modifications in normal mechanisms of cell signaling. DNA mutation can result in a number of genetic abnormalities such as cancer, heart failure, Alzheimer’s disease, and depression. Human body has special protection in the form of antioxidant molecules and enzymes against these free radicals. Generation of ROS and its neutralization must be regulated to protect cells and signalling biomolecules from the deleterious effect of oxidative stress with the involvement of antioxidant systems, enzymes, and specific proteins. DNA repair system is a complex system which helps in the identification, removal of the wrong nucleotide and repairs them and as a result, the cell will produce correct and functional protein and active enzyme.

Keywords: Free radical, oxidative, ROS, superoxide, DNA damage, DNA repair.

Graphical Abstract
Cabiscol E, Tamarit J, Ros J. Oxidative stress in bacteria and protein damage by reactive oxygen species. Int Microbiol 2000; 3(1): 03-8.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010; 49(11): 1603-16.
Strauss BS. DNA repair mechanisms and their relation to mutation and recombination. Curr Top Microbiol Immunol 1968; 44: 1-85.
Friedberg EC. DNA damage and repair. Nature 2003; 421(6921): 436-40.
Ward JF. DNA damage and repair. In: Glass WA, Varma MN, Eds. Physical and chemical mechanisms in molecular radiation biology.Boston, MA: Springer. 1991; pp. 403-21.
Nita M, Grzybowski A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid Med Cell Longev 2016; 20163164734
Sies H. What is oxidative stress? In: Keaney Jr, John F, Eds. Oxidative stress and vascular disease.Boston, MA: Springer. 2000; pp. 1-8.
Sies H. Biochemistry of oxidative stress. Angewandte Chemie Int 1986; 25(12): 1058-71.
Apel K, Hirt H. Reactive oxygen species: Metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 2004; 55: 373-99.
Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74(1): 139-62.
Halliwell B. Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence? The Lancet 1994; 344(8924): 721-4.
Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 2003; 27: 277-84.
Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005; 12(10): 1161-208.
Conklin KA. Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness. Integr Cancer Ther 2004; 3(4): 294-300.
Logan AC, Wong C. Chronic fatigue syndrome: Oxidative stress and dietary modifications. Altern Med Rev 2001; 6(5): 450-9.
Kryston TB, Georgiev AB, Pissis P, Georgakilas AG. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 2011; 711(1): 193-201.
Halliwell B. Oxidants and human disease: Some new concepts. The FASEB J 1987; 1(5): 358-64.
Essick EE, Sam F. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging, and cancer. Oxid Med Cell Longev 2010; 3(3): 168-77.
Repine JE, Bast A, Lankhorst IDA. Oxidative stress study group oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156(2): 341-57.
Mapp PI, Grootveld MC, Blake DR. Hypoxia, oxidative stress, and rheumatoid arthritis. Br Med Bull 1995; 51(2): 419-36.
Small DM, Coombes JS, Bennett N, Johnson DW, Gobe GC. Oxidative stress, anti‐oxidant therapies, and chronic kidney disease. Nephrol 2012; 17(4): 311-21.
Spector A. Oxidative stress and disease. J Ocul Pharmacol Ther 2012; 16(2): 193-201.
Harman D. Aging and oxidative stress. J Int Fed Clin Chem 1998; 10(1): 24-7.
Riley PA. Free radicals in biology: Oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994; 65(1): 27-33.
Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995; 41(12): 1819-28.
Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997; 272(33): 20313-6.
Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Nat Acad Sci 1997; 94(2): 514-9.
Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat Res 1997; 387(3): 147-63.
Slupphaug G, Kavli B, Krokan HE. The interacting pathways for prevention and repair of oxidative DNA damage. Mutat Res 2003; 531(1): 231-51.
Hemnani T, Parihar MS. Reactive oxygen species and oxidative DNA damage. Indian J Physiol Pharmacol 1998; 42(4): 440-52.
Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions. J Biol Chem 1992; 267(1): 166-72.
Kawanishi S, Hiraku Y, Oikawa S. Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging. Mutat Res 2001; 488(1): 65-76.
Lu AL, Li X, Gu Y, Wright PM, Chang DY. Repair of oxidative DNA damage. Cell Biochem Biophys 2001; 35(2): 141-70.
David SS, O’Shea VL, Kundu S. Base-excision repair of oxidative DNA damage. Nature 2007; 447(7147): 941-50.
Svilar D, Goellner EM, Almeida KH, Sobol RW. Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage. Antioxid Redox Signal 2011; 14(12): 2491-507.
Dizdaroglu M. Base-excision repair of oxidative DNA damage by DNA glycosylases. Mutat Res 2005; 591(1): 45-59.
Szczesny B, Tann AW, Longley MJ, Copeland WC, Mitra S. Long patch base excision repair in mammalian mitochondrial genomes. J Biol Chem 2008; 283(39): 26349-56.
Hegde ML, Hazra TK, Mitra S. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 2008; 18(1): 27-47.
Kuraoka I, Bender C, Romieu A, Cadet J, Wood RD, Lindahl T. Removal of oxygen free-radical-induced 5′, 8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc Natl Acad Sci 2000; 97(8): 3832-7.
de Laat WL, Jaspers NG, Hoeijmakers JH. Molecular mechanism of nucleotide excision repair. Genes Dev 1999; 13(7): 768-85.
O’Donovan A, Davies AA, Moggs JG, West SC, Wood RD. XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair. Nature 1994; 371(6496): 432-5.
Wojcik KA, Kaminska A, Blasiak J, Szaflik J, Szaflik JP. Oxidative stress in the pathogenesis of keratoconus and Fuchs endothelial corneal dystrophy. Int J Mol Sci 2013; 14(9): 19294-308.

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