Abstract
One of the unique features of mitochondria is that these organelles possess their own DNA (mtDNA). The mitochondrial genome, like any DNA is subject to continuous attack on its integrity from both endogenous and exogenous sources. In order to understand the consequences of such an attack, one must consider key aspects of mtDNA organization and maintenance. Mammalian cells contain one to several thousand copies of mtDNA per cell, which are characterized as being enclosed in multiple mitochondria at 1 to 11 copies per organelle (Cavelier et al. 2000). Human mtDNA is a circular negatively supercoiled double-stranded molecule that is 16,569 bp long (Figure 15.1). It encodes 13 polypeptides, 22 tRNAs and 2 rRNAs.
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References
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP (2002) Inherited variants of MYH associated with somatic G:C—T:A mutations in colorectal tumors. Nat Genet 30: 227–232
Allen JA, Coombs MM Covalent binding of polycyclic aromatic compounds to mitochondrial and nuclear DNA (1980) Nature 287: 244–245
Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 90: 7915–7922
Anderson CT, Friedberg EC (1980) The presence of nuclear and mitochondrial uracil-DNA glycosylase in extracts of human KB cells. Nucleic Acids Res 8: 875–888
Anson RM, Hudson E, Bohr VA (2000) Mitochondrial endogenous oxidative damage has been overestimated. FASEB J 14: 355–360
Asagoshi K, Yamada T, Okada Y, Terato H, Ohyama Y, Seki S, Ide H (2000) Recognition of formamidopyrimidine by Escherichia coli and mammalian thymine glycol glycosylases. Distinctive paired base effects and biological and mechanistic implications. J Biol Chem 275: 24781–24786
Aspinwall R, Rothwell DG, Roldan-Arjona T, Anselmino C, Ward CJ, Cheadle J P, Sampson JR, Lindahl T, Harris PC, Hickson ID (1997) Cloning and characterization of a functional human homolog of Escherichia coli endonuclease III. Proc Natl Acad Sci USA 94: 109–114
Attardi G, Schatz G (1988) Biogenesis of mitochondria. Annu Rev Cell Biol 4: 289–333
Backer JM, Weinstein IB (1980) Mitochondrial DNA is a major cellular target for a dihydrodiol-epoxide derivative of benzo[a]pyrene. Science 209: 297–299
Beckman KB, Ames BN (1999) Endogenous oxidative damage of mtDNA. Mutat Res 424: 51–58
Bjelland S, Seeberg E (2003) Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat Res 531: 37–80
Bogenhagen DF, Pinz KG, Perez-Jannotti RM (2001) Enzymology of mitochondrial base excision repair. Prog Nucleic Acid Res Mol Biol 68: 257–271
Bogenhagen DF, Wang Y, Shen EL, Kobayashi R (2003) Protein components of mitochondrial DNA nucleoids in higher eukaryotes. Mol Cell Proteomics 2: 1205–1216
Bohr VA, Stevnsner T, de Souza-Pinto NC (2002) Mitochondrial DNA repair of oxidative damage in mammalian cells. Gene 286: 127–134
Boiteux S, Radicella JP (2000) The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. Arch Biochem Biophys 377: 1–8
Brown WM, George M Jr, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76: 1967–1971
Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29: 222–230
Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, Sauvaigo S (1999) Hydroxyl radicals and DNA base damage. Mutat Res 424: 9–21
Cavelier L, Johannisson A, Gyllensten U (2000) Analysis of mtDNA copy number and composition of single mitochondrial particles using flow cytometry and PCR. Exp Cell Res 259: 79–85
Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA (1992) 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G—-T and A—-C substitutions. J Biol Chem 267: 166–172
Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193: 3–34
Clayton DA, Doda JN, Friedberg EC (1974) The absence of a pyrimidine dimer repair mechanism in mammalian mitochondria. Proc Natl Acad Sci USA 71: 2777–2781
Collins AR, Cadet J, Moller L, Poulsen HE, Vina J (2004) Are we sure we know how to measure 8-oxo-7,8-dihydroguanine in DNA from human cells? Arch Biochem Biophys 423: 57–65
Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17: 1195–1214
Copeland WC, Longley MJ (2003) DNA polymerase gamma in mitochondrial DNA replication and repair. Scientific World Journal 3: 34–44
Copeland WC, Wachsman JT, Johnson FM, Penta JS (2002) Mitochondrial DNA alterations in cancer. Cancer Invest 20: 557–569
Croteau DL, Stierum RH, Bohr VA (1999) Mitochondrial DNA repair pathways. Mutat Res 434: 137–148
de Souza-Pinto NC, Eide L, Hogue BA, Thybo T, Stevnsner T, Seeberg E, Klungland A, Bohr VA (2001) Repair of 8-oxodeoxyguanosine lesions in mitochondrial dna depends on the oxoguanine DNA glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial dna of OGG1-defective mice. Cancer Res 61: 5378–5381
DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348: 2656–2668
Dizdaroglu M (2005) Base-excision repair of oxidative DNA damage by DNA glycosylases. Mutat Res 591:45–59
Dizdaroglu M (1998) Mechanisms of free radical damage to DNA. In: O. I. H. Aruoma (ed.), DNA & Free Radicals: Techniques, Mechanisms & Applications, pp. 3–26. Saint Lucia: OICA International
Dobson AW, Grishko V, LeDoux SP, Kelley MR, Wilson GL, Gillespie MN (2002) Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol 283: L205–210
Dobson AW, Xu Y, Kelley MR, LeDoux SP, Wilson GL (2000) Enhanced mitochondrial DNA repair and cellular survival after oxidative stress by targeting the human 8-oxoguanine glycosylase repair enzyme to mitochondria. J Biol Chem 275: 37518–37523
Doroshow JH, Davies KJ (1986) Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J Biol Chem 261: 3068–3074
Driggers WJ, LeDoux SP, Wilson GL (1993) Repair of oxidative damage within the mitochondrial DNA of RINr 38 cells. J Biol Chem 268: 22042–22045
Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95
Druzhyna NM, Hollensworth SB, Kelley MR, Wilson GL, Ledoux SP (2003) Targeting human 8-oxoguanine glycosylase to mitochondria of oligodendrocytes protects against menadione-induced oxidative stress. Glia 42: 370–378
Durham SE, Krishnan KJ, Betts J, Birch-Machin MA (2003) Mitochondrial DNA damage in non-melanoma skin cancer. Br J Cancer 88: 90–95
ESCODD (2002) Comparative analysis of baseline 8-oxo-7,8-dihydroguanine in mammalian cell DNA, by different methods in different laboratories: an approach to consensus. Carcinogenesis 23: 2129–2133
ESCODD (2003) Measurement of DNA oxidation in human cells by chromatographic and enzymic methods. Free Radic Biol Med 34: 1089–1099
Fishel ML, Seo YR, Smith ML, Kelley MR (2003) Imbalancing the DNA base excision repair pathway in the mitochondria; targeting and overexpressing N-methylpurine DNA glycosylase in mitochondria leads to enhanced cell killing. Cancer Res 63: 608615
Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, Jen J, Sidransky D (2000) Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287: 2017–2019
Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN (2003) Composition and dynamics of human mitochondrial nucleoids. Mol Biol Cell 14: 1583–1596
Geromel V, Kadhom N, Cebalos-Picot I, Ouari O, Polidori A, Munnich A, Rotig A, Rustin P (2001) Superoxide-induced massive apoptosis in cultured skin fibroblasts harboring the neurogenic ataxia retinitis pigmentosa (NARP) mutation in the ATPase-6 gene of the mitochondrial DNA. Hum Mol Genet 10: 1221–1228
Graziewicz MA, Day BJ, Copeland WC (2002) The mitochondrial DNA polymerase as a target of oxidative damage. Nucleic Acids Res 30: 2817–2824
Grollman AP, Moriya M (1993) Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet 9: 246–249
Gross NJ, Getz GS, Rabinowitz M (1969) Apparent turnover of mitochondrial deoxyribonucleic acid and mitochondrial phospholipids in the tissues of the rat. J Biol Chem 244: 1552–1562
Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, Troyer DA, Thompson I, Richardson AA (2001) Reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA. Nucleic Acids Res 29: 2117–2126
Helbock HJ, Beckman KB, Shigenaga MK, Walter PB, Woodall AA, Yeo, HC, Ames BN (1998) DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine. Proc Natl Acad Sci USA 95: 288-293
Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW (1997) Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III. J Biol Chem 272: 6733–6740
Hollensworth SB, Shen C, Sim JE, Spitz DR, Wilson GL, LeDoux SP (2000) Glial cell type-specific responses to menadione-induced oxidative stress. Free Radic Biol Med 28: 1161–1174
Holt IJ, Harding AE, Morgan-Hughes JA (1998) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331: 717–719
Ikeda S, Biswas T, Roy R, Izumi T, Boldogh I, Kurosky A, Sarker AH, Seki S, Mitra S (1998) Purification and characterization of human NTH1, a homolog of Escherichia coli endonuclease III. Direct identification of Lys-212 as the active nucleophilic residue. J Biol Chem 273: 21585–21593
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002) Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C–>T:A mutations. Hum Mol Genet 11: 2961–2967
Kaguni LS (2004) DNA polymerase gamma, the mitochondrial replicase. Annu Rev Biochem 73: 293–320
Kang D, Hamasaki N (2005) Alterations of mitochondrial DNA in common diseases and disease states: aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 12: 429–441
Kang D, Nishida J, Iyama A, Nakabeppu Y, Furuichi M, Fujiwara T, Sekiguchi M, Takeshige K (1995) Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria. J Biol Chem 270: 14659–14665
Karahalil B, de Souza-Pinto NC, Parsons JL, Elder RH, Bohr VA (2003) Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases. J Biol Chem 278: 33701–33707
Khrapko K, Coller HA, Andre PC, Li XC, Hanekamp JS, Thilly WG (1997) Mitochondrial mutational spectra in human cells and tissues. Proc Natl Acad Sci USA 94: 13798–13803
Klein JC, Bleeker MJ, Saris CP, Roelen HC, Brugghe HF, van den Elst H, van der Marel GA, van Boom JH, Westra JG, Kriek E, Berens AJM (1992) Repair and replication of plasmids with site-specific 8-oxodG and 8-AAFdG residues in normal and repair-deficient human cells. Nucleic Acids Res 20: 4437–4443
Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B, Seeberg E, Lindahl T, Barnes DE (1999) Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci USA 96: 13300–13305
Korhonen JA, Pham XH, Pellegrini M, Falkenberg M (2004) Reconstitution of a minimal mtDNA replisome in vitro. Embo J 23: 2423–2429
Krokan HE, Otterlei M, Nilsen H, Kavli B, Skorpen F, Andersen S, Skjelbred C, Akbari M, Aas PA, Slupphaug G (2001) Properties and functions of human uracil-DNA glycosylase from the UNG gene. Prog Nucleic Acid Res Mol Biol 68: 365–386
Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481–484
Kunishige M, Mitsui T, Akaike M, Kawajiri M, Shono M, Kawai H, Matsumoto T (2003) Overexpressions of myoglobin and antioxidant enzymes in ragged-red fibers of skeletal muscle from patients with mitochondrial encephalomyopathy. Muscle Nerve 28: 484–492
Lakshmipathy U, Campbell C (2001) Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity. Nucleic Acids Res 29: 668–676
Lakshmipathy U, Campbell C (2000) Mitochondrial DNA ligase III function is independent of Xrcc1. Nucleic Acids Res 28: 3880–3886
Lakshmipathy U, Campbell C (1999) The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol Cell Biol 19: 3869–3876
Le Page F, Margot A, Grollman AP, Sarasin A, Gentil A (1995) Mutagenicity of a unique 8-oxoguanine in a human Ha-ras sequence in mammalian cells. Carcinogenesis 16: 2779–2784
LeDoux SP, Driggers WJ, Hollensworth BS, Wilson GL (1999) Repair of alkylation and oxidative damage in mitochondrial DNA. Mutat Res 434: 149–159
Ledoux SP, Shen CC, Grishko VI, Fields PA, Gard AL, Wilson GL (1998) Glial cell-specific differences in response to alkylation damage. Glia 24: 304–312
LeDoux SP, Wilson GL, Beecham EJ, Stevnsner T, Wassermann K, Bohr VA (1992) Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells. Carcinogenesis 13: 1967–1973
Legros F, Malka F, Frachon P, Lombes A, Rojo M (2004) Organization and dynamics of human mitochondrial DNA. J Cell Sci 117: 2653–2662
Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 1: 885
Lim KS, Jeyaseelan K, Whiteman M, Jenner A, Halliwell B (2005) Oxidative damage in mitochondrial DNA is not extensive. Ann N Y Acad Sci 1042: 210–220
Longley MJ, Prasad R, Srivastava DK, Wilson SH, Copeland WC (1998) Identification of 5’-deoxyribose phosphate lyase activity in human DNA polymerase gamma and its role in mitochondrial base excision repair in vitro. Proc Natl Acad Sci USA 95: 12244–12248
Lu CY, Wang EK, Lee HC, Tsay HJ, Wei YH (2003) Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome. Mol Genet Metab 80: 321–329
Lu R, Nash HM, Verdine GLA (1997) Mammalian DNA repair enzyme that excises oxidatively damaged guanines maps to a locus frequently lost in lung cancer. Curr Biol 7: 397–407
Luna L, Bjoras M, Hoff E, Rognes T, Seeberg E (2000) Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA. Mutat Res 460: 95–104
Magana-Schwencke N, Henriques J A, Chanet R, Moustacchi E The fate of 8-methoxypsoralen photoinduced crosslinks in nuclear and mitochondrial yeast DNA: comparison of wild-type and repair-deficient strains. Proc Natl Acad Sci U S A 79: 1722–1726, 1982
Mambo E, Gao X, Cohen Y, Guo Z, Talalay P, Sidransky D (2003) Electrophile and oxidant damage of mitochondrial DNA leading to rapid evolution of homoplasmic mutations. Proc Natl Acad Sci USA 100: 1838-1843
Martinez GR, Loureiro AP, Marques SA, Miyamoto S, Yamaguchi LF, Onuki J, Almeida EA, Garcia CC, Barbosa LF, Medeiros MH, Di Mascio P (2003) Oxidative and alkylating damage in DNA. Mutat Res 544: 115–127
Miyaki M, Yatagai K, Ono T (1977) Strand breaks of mammalian mitochondrial DNA induced by carcinogens. Chem Biol Interact 17: 321–329
Moriya M (1993) Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G.C–>T.A transversions in simian kidney cells. Proc Natl Acad Sci USA 90: 1122-1126
Moriya M, Ou C, Bodepudi V, Johnson F, Takeshita M, Grollman AP (1991) Site-specific mutagenesis using a gapped duplex vector: a study of translesion synthesis past 8-oxodeoxyguanosine in E. coli. Mutat Res 254: 281–288
Nakabeppu Y (2001) Molecular genetics and structural biology of human MutT homolog, MTH1. Mutat Res 477: 59–70
Nakabeppu Y (2001) Regulation of intracellular localization of human MTH1, OGG1, and MYH proteins for repair of oxidative DNA damage. Prog Nucleic Acid Res Mol Biol 68: 75–94
Nakabeppu Y, Tsuchimoto D, Ichinoe A, Ohno M, Ide Y, Hirano S, Yoshimura D, Tominaga Y, Furuichi M, Sakumi K (2004) Biological significance of the defense mechanisms against oxidative damage in nucleic acids caused by reactive oxygen species: from mitochondria to nuclei. Ann N Y Acad Sci 1011: 101–111
Neubert D, Hopfenmuller W, Fuchs G (1981) Manifestation of carcinogenesis as a stochastic process on the basis of an altered mitochondrial genome. Arch Toxicol 48: 89–125
Nilsen H, Rosewell I, Robins P, Skjelbred CF, Andersen S, Slupphaug G, Daly G, Krokan HE, Lindahl T, Barnes DE (2000) Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol Cell 5: 1059–1065
Niranjan BG, Bhat NK, Avadhani NG (1982) Preferential attack of mitochondrial DNA by aflatoxin B1 during hepatocarcinogenesis. Science 215: 73–75
Nishioka K, Ohtsubo T, Oda H, Fujiwara T, Kang D, Sugimachi K, Nakabeppu Y (1999) Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs. Mol Biol Cell 10: 1637–1652
Ocampo MT, Chaung W, Marenstein DR, Chan MK, Altamirano A, Basu AK, Boorstein RJ, Cunningham RP, Teebor GW (2002) Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity. Mol Cell Biol 22: 6111-6121
Ohtsubo T, Nishioka K, Imaiso Y, Iwai S, Shimokawa H, Oda H, Fujiwara T, Nakabeppu Y (2000) Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria. Nucleic Acids Res 28: 1355–1364
Parker A, Gu Y, Lu AL (2000) Purification and characterization of a mammalian homolog of Escherichia coli MutY mismatch repair protein from calf liver mitochondria. Nucleic Acids Res 28: 3206–3215
Pavlov YI, Minnick DT, Izuta S, Kunkel TA (1994) DNA replication fidelity with 8-oxodeoxyguanosine triphosphate. Biochemistry 33: 4695–4701
Pelicano H, Carney D, Huang P (2004) ROS stress in cancer cells and therapeutic implications. Drug Resist Updat 7: 97–110
Petros JA, Baumann AK, Ruiz-Pesini E, Amin MB, Sun CQ, Hall J, Lim S, Issa MM, Flanders WD, Hosseini SH, Marshall FF, Wallace DC (2005) mtDNA mutations increase tumorigenicity in prostate cancer. Proc Natl Acad Sci USA 102: 719–724
Pettepher CC, LeDoux SP, Bohr VA, Wilson GL (1991) Repair of alkali-labile sites within the mitochondrial DNA of RINr 38 cells after exposure to the nitrosourea streptozotocin. J Biol Chem 266: 3113–3117
Pinz KG, Bogenhagen DF (2000) Characterization of a catalytically slow AP lyase activity in DNA polymerase gamma and other family A DNA polymerases. J Biol Chem 275: 12509–12514
Pinz KG, Bogenhagen DF (1998) Efficient repair of abasic sites in DNA by mitochondrial enzymes. Mol Cell Biol 18: 1257–1265
Pinz KG, Shibutani S, Bogenhagen DF (1995) Action of mitochondrial DNA polymerase gamma at sites of base loss or oxidative damage. J Biol Chem 270: 9202–9206
Pirsel M, Bohr VA (1993) Methyl methanesulfonate adduct formation and repair in the DHFR gene and in mitochondrial DNA in hamster cells. Carcinogenesis 14: 2105–2108
Polyak K, Li Y, Zhu H, Lengauer C, Willson JK, Markowitz SD, Trush MA, Kinzler KW, Vogelstein B (1998) Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet 20: 291–293
Rachek LI, Grishko VI, Alexeyev MF, Pastukh VV, LeDoux SP, Wilson, GL (2004) Endonuclease III and endonuclease VIII conditionally targeted into mitochondria enhance mitochondrial DNA repair and cell survival following oxidative stress. Nucleic Acids Res 32: 3240–3247
Rachek LI, Grishko VI, Musiyenko SI, Kelley MR, LeDoux SP, Wilson GL (2002) Conditional targeting of the DNA repair enzyme hOGG1 into mitochondria. J Biol Chem 277: 44932–44937
Raha S, Robinson BH (2000) Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 25: 502–508
Richter C, Park JW, Ames BN (1998) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 85: 6465–6467
Rossi SC, Gorman N, Wetterhahn KE (1988) Mitochondrial reduction of the carcinogen chromate: formation of chromium(V). Chem Res Toxicol 1: 101–107
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73: 39–85
Sawyer DE, Van Houten B (1999) Repair of DNA damage in mitochondria. Mutat Res 434: 161–176
Scharer OD (2003) Chemistry and biology of DNA repair. Angew Chem Int Ed Engl 42: 2946–2974
Senturker S, Dizdaroglu M (1999) The effect of experimental conditions on the levels of oxidatively modified bases in DNA as measured by gas chromatography-mass spectrometry: how many modified bases are involved? Prepurification or not? Free Radic Biol Med 27: 370–380
Shadel GS, Clayton DA (1997) Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem 66: 409–435
Shokolenko IN, Alexeyev MF, LeDoux SP, Wilson GL (2005) TAT-mediated protein transduction and targeted delivery of fusion proteins into mitochondria of breast cancer cells. DNA Repair (Amst) 4: 511–518
Shokolenko IN, Alexeyev MF, Robertson FM, LeDoux SP, Wilson GL (2003) The expression of Exonuclease III from E. coli in mitochondria of breast cancer cells diminishes mitochondrial DNA repair capacity and cell survival after oxidative stress. DNA Repair (Amst) 2: 471–482
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348: 791–799
Singer TP, Ramsay RR (1990) Mechanism of the neurotoxicity of MPTP. An update. FEBS Lett 274: 1–8
Starkov AA, Fiskum G, Chinopoulos C, Lorenzo BJ, Browne SE, Patel MS, Beal MF (2004) Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci 24: 7779–7788
Steenken S (1997) Electron transfer in DNA? Competition by ultra-fast proton transfer? Biol Chem 378: 1293–1297
Stierum RH, Dianov GL, Bohr VA (1999) Single-nucleotide patch base excision repair of uracil in DNA by mitochondrial protein extracts. Nucleic Acids Res 27: 3712–3719
Szczesny B, Hazra TK, Papaconstantinou J, Mitra S, Boldogh I (2003) Age-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases. Proc Natl Acad Sci USA 100: 10670–10675
Taanman JW (1999) The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta 1410: 103–123
Takao M, Aburatani H, Kobayashi K, Yasui A (1998) Mitochondrial targeting of human DNA glycosylases for repair of oxidative DNA damage. Nucleic Acids Res 26: 2917–2922
Takao M, Kanno S, Shiromoto T, Hasegawa R, Ide H, Ikeda S, Sarker AH, Seki S, Xing JZ, Le XC, Weinfeld M, Kobayashi K, Miyazaki J, Muijtjens M, Hoeijmakers JH, van der Horst G, Yasui A (2002) Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III homolog for repair of thymine glycols. Embo J 21: 3486–3493
Takayama S, Muramatsu M (1969) Incorporation of tritiated dimethylnitrosamine into subcellular fractions of mouse liver after long term administration of dimethylnitrosamine. Z Krebsforsch 73: 172–179
Tomasi A, Albano E, Banni S, Botti B, Corongiu F, Dessi MA, Iannone A, Vannini V, Dianzani MU (1987) Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation. Biochem J 246: 313–317
Tretter L, Adam-Vizi V (2004) Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase. J Neurosci 24: 7771–7778
Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom, R, Tornell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429: 417–423
Tsuzuki T, Egashira A, Igarashi H, Iwakuma T, Nakatsuru Y, Tominaga Y, Kawate H, Nakao K, Nakamura K, Ide F, Kura S, Nakabeppu Y, Katsuki M, Ishikawa T, Sekiguchi M (2001) Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase. Proc Natl Acad Sci USA 98: 11456–11461
Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang TT, Nelson J, Strong R, Richardson A (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16: 29–37
Wadia JS, Dowdy SF (2005) Transmembrane delivery of protein and peptide drugs by TAT-mediated transduction in the treatment of cancer. Adv Drug Deliv Rev 57: 579–596
Wallace DCA (2005) Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine. Annu Rev Genet 39:359–407
Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ (1988) 2nd, Nikoskelainen E K Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242: 1427–1430
Wallace SS (1998) Enzymatic processing of radiation-induced free radical damage in DNA. Radiat Res 150: S60–79
Wood ML, Dizdaroglu M, Gajewski E, Essigmann JM (1990) Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry 29: 7024–7032
Wunderlich V, Schutt M, Bottger M, Graffi A (1970) Preferential alkylation of mitochondrial deoxyribonucleic acid by N-methyl-N-nitrosourea. Biochem J 118: 99–109
Yakes FM, Van Houten B (1997) Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94: 514–519
Yakubovskaya E, Chen Z, Carrodeguas JA, Kisker C, Bogenhagen DF (2006) Functional human mitochondrial DNA polymerase gamma forms a heterotrimer. J Biol Chem 281: 374–382
Yang MY, Bowmaker M, Reyes A, Vergani L, Angeli P, Gringeri E, Jacobs H T, Holt IJ (2002) Biased incorporation of ribonucleotides on the mitochondrial L-strand accounts for apparent strand-asymmetric DNA replication. Cell 111: 495–505
Yoneda M, Katsumata K, Hayakawa M, Tanaka M, Ozawa T (1995) Oxygen stress induces an apoptotic cell death associated with fragmentation of mitochondrial genome. Biochem Biophys Res Commun 209: 723–729
Zastawny TH, Dabrowska M, Jaskolski T, Klimarczyk M, Kulinski L, Koszela A, Szczesniewicz M, Sliwinska M, Witkowski P, Olinski R (1998) Comparison of oxidative base damage in mitochondrial and nuclear DNA. Free Radic Biol Med 24: 722–725
Zhang D, Mott JL, Farrar P, Ryerse JS, Chang SW, Stevens M, Denniger G, Zassenhaus HP (2003) Mitochondrial DNA mutations activate the mitochondrial apoptotic pathway and cause dilated cardiomyopathy. Cardiovasc Res 57: 147–157
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Shokolenko, I.N., Ledoux, S.P., Wilson, G.L. (2007). Mitochondrial DNA Damage and Repair. In: Schaffer, S.W., Suleiman, MS. (eds) Mitochondria. Advances in Biochemistry in Health and Disease, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69945-5_15
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DOI: https://doi.org/10.1007/978-0-387-69945-5_15
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