Abstract
Base excision DNA repair (BER) is a vitally important pathway that protects the cell genome from many kinds of DNA damage, including oxidation, deamination, and hydrolysis. It involves several tightly coordinated steps, starting from damaged base excision and followed by nicking one DNA strand, incorporating an undamaged nucleotide, and DNA ligation. Deficiencies in BER are often embryonic lethal or cause morbid diseases such as cancer, neurodegeneration, or severe immune pathologies. Starting from the early 1980s, when the first mammalian cell lines lacking BER were produced by spontaneous mutagenesis, such lines have become a treasure trove of valuable information about the mechanisms of BER, often revealing unexpected connections with other cellular processes, such as antibody maturation or epigenetic demethylation. In addition, these cell lines have found an increasing use in genotoxicity testing, where they provide increased sensitivity and representativity to cell-based assay panels. In this review, we outline current knowledge about BER-deficient cell lines and their use.
Keywords: DNA repair, base excision repair, knockout cell lines, genotoxicity assays, mutagenesis, epigenetic demethylation.
[1]
De Bont R, van Larebeke N. Endogenous DNA damage in humans: A review of quantitative data. Mutagenesis 2004; 19(3): 169-85.
[2]
Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 2009; 461(7267): 1071-8.
[3]
Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010; 40(2): 179-204.
[4]
Tubbs A, Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 2017; 168(4): 644-56.
[5]
O’Driscoll M. Diseases associated with defective responses to DNA damage. Cold Spring Harb Perspect Biol 2012; 4(12)A012773
[6]
Keijzers G, Bakula D, Scheibye-Knudsen M. Monogenic diseases of DNA repair. N Engl J Med 2017; 377(19): 1868-76.
[7]
Lindahl T. Suppression of spontaneous mutagenesis in human cells by DNA base excision-repair. Mutat Res 2000; 462(2-3): 129-35.
[9]
Podlutsky AJ, Dianova II, Podust VN, Bohr VA, Dianov GL. Human DNA polymerase β initiates DNA synthesis during long-patch repair of reduced AP sites in DNA. EMBO J 2001; 20(6): 1477-82.
[10]
Fortini P, Dogliotti E. Base damage and single-strand break repair: mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair (Amst) 2007; 6(4): 398-409.
[11]
Robertson AB, Klungland A, Rognes T, Leiros I. Base excision repair: the long and short of it. Cell Mol Life Sci 2009; 66(6): 981-93.
[12]
Ischenko AA, Saparbaev MK. Alternative nucleotide incision repair pathway for oxidative DNA damage. Nature 2002; 415(6868): 183-7.
[13]
Wiederhold L, Leppard JB, Kedar P, et al. AP endonuclease-independent DNA base excision repair in human cells. Mol Cell 2004; 15(2): 209-20.
[14]
Franchini D-M, Schmitz K-M, Petersen-Mahrt SK. 5-Methylcytosine DNA demethylation: more than losing a methyl group. Annu Rev Genet 2012; 46: 419-41.
[15]
Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 2017; 18(9): 517-34.
[16]
Di Noia JM, Neuberger MS. Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem 2007; 76: 1-22.
[17]
Matthews AJ, Zheng S, DiMenna LJ, Chaudhuri J. Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair. Adv Immunol 2014; 122: 1-57.
[18]
Wood RD, Coverley D. DNA excision repair in mammalian cell extracts. BioEssays 1991; 13(9): 447-53.
[19]
Cleaver JE, Thompson LH, Richardson AS, States JC. A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat 1999; 14(1): 9-22.
[20]
Carette JE, Raaben M, Wong AC, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 2011; 477(7364): 340-3.
[21]
Biard DSF. Untangling the relationships between DNA repair pathways by silencing more than 20 DNA repair genes in human stable clones. Nucleic Acids Res 2007; 35(11): 3535-50.
[22]
Krokan HE, Drabløs F, Slupphaug G. Uracil in DNA-occurrence, consequences and repair. Oncogene 2002; 21(58): 8935-48.
[23]
Kavli B, Otterlei M, Slupphaug G, Krokan HE. Uracil in DNA-general mutagen, but normal intermediate in acquired immunity. DNA Repair (Amst) 2007; 6(4): 505-16.
[24]
Nilsen H, Otterlei M, Haug T, et al. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic Acids Res 1997; 25(4): 750-5.
[25]
Haug T, Skorpen F, Aas PA, Malm V, Skjelbred C, Krokan HE. Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase. Nucleic Acids Res 1998; 26(6): 1449-57.
[26]
Otterlei M, Haug T, Nagelhus TA, Slupphaug G, Lindmo T, Krokan HE. Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localisation signal and a strong classical mitochondrial localisation signal, respectively. Nucleic Acids Res 1998; 26(20): 4611-7.
[27]
Imai K, Slupphaug G, Lee W-I, et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 2003; 4(10): 1023-8.
[28]
Kavli B, Andersen S, Otterlei M, et al. B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. J Exp Med 2005; 201(12): 2011-21.
[29]
Nilsen H, Rosewell I, Robins P, et al. Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol Cell 2000; 5(6): 1059-65.
[30]
Endres M, Biniszkiewicz D, Sobol RW, et al. Increased postischemic brain injury in mice deficient in uracil-DNA glycosylase. J Clin Invest 2004; 113(12): 1711-21.
[31]
Rada C, Williams GT, Nilsen H, Barnes DE, Lindahl T, Neuberger MS. Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr Biol 2002; 12(20): 1748-55.
[32]
Nilsen H, Stamp G, Andersen S, et al. Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas. Oncogene 2003; 22(35): 5381-6.
[33]
Andersen S, Ericsson M, Dai HY, et al. Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice. DNA Repair (Amst) 2005; 4(12): 1432-41.
[34]
Kronenberg G, Harms C, Sobol RW, et al. Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase. J Neurosci 2008; 28(28): 7219-30.
[35]
Nilsen H, Haushalter KA, Robins P, Barnes DE, Verdine GL, Lindahl T. Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase. EMBO J 2001; 20(15): 4278-86.
[36]
Begum NA, Izumi N, Nishikori M, Nagaoka H, Shinkura R, Honjo T. Requirement of non-canonical activity of uracil DNA glycosylase for class switch recombination. J Biol Chem 2007; 282(1): 731-42.
[37]
Di Noia J, Neuberger MS. Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 2002; 419(6902): 43-8.
[38]
Saribasak H, Saribasak NN, Ipek FM, Ellwart JW, Arakawa H, Buerstedde J-M. Uracil DNA glycosylase disruption blocks Ig gene conversion and induces transition mutations. J Immunol 2006; 176(1): 365-71.
[39]
Begum NA, Kinoshita K, Kakazu N, et al. Uracil DNA glycosylase activity is dispensable for immunoglobulin class switch. Science 2004; 305(5687): 1160-3.
[40]
Methot SP, Di Noia JM. Molecular mechanisms of somatic hypermutation and class switch recombination. Adv Immunol 2017; 133: 37-87.
[41]
Neddermann P, Jiricny J. The purification of a mismatch-specific thymine-DNA glycosylase from HeLa cells. J Biol Chem 1993; 268(28): 21218-24.
[42]
Neddermann P, Gallinari P, Lettieri T, et al. Cloning and expression of human G/T mismatch-specific thymine-DNA glycosylase. J Biol Chem 1996; 271(22): 12767-74.
[43]
Bochtler M, Kolano A, Xu G-L. DNA demethylation pathways: Additional players and regulators. BioEssays 2017; 39(1): 1-13.
[44]
Cortázar D, Kunz C, Selfridge J, et al. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability. Nature 2011; 470(7334): 419-23.
[45]
Kunz C, Focke F, Saito Y, et al. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil. PLoS Biol 2009; 7(4)e91
[46]
Haushalter KA, Todd Stukenberg MW, Kirschner MW, Verdine GL. Identification of a new uracil-DNA glycosylase family by expression cloning using synthetic inhibitors. Curr Biol 1999; 9(4): 174-85.
[47]
Kavli B, Sundheim O, Akbari M, et al. hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. J Biol Chem 2002; 277(42): 39926-36.
[48]
Visnes T, Doseth B, Pettersen HS, et al. Uracil in DNA and its processing by different DNA glycosylases. Philos Trans R Soc Lond B Biol Sci 2009; 364(1517): 563-8.
[49]
Olinski R, Starczak M, Gackowski D. Enigmatic 5-hydroxymethyluracil: Oxidatively modified base, epigenetic mark or both? Mutat Res Rev Mutat Res 2016; 767: 59-66.
[50]
Kemmerich K, Dingler FA, Rada C, Neuberger MS. Germline ablation of SMUG1 DNA glycosylase causes loss of 5-hydroxymethyluracil- and UNG-backup uracil-excision activities and increases cancer predisposition of Ung-/-Msh2-/- mice. Nucleic Acids Res 2012; 40(13): 6016-25.
[51]
Alsøe L, Sarno A, Carracedo S, et al. Uracil accumulation and mutagenesis dominated by cytosine deamination in CpG dinucleotides in mice lacking UNG and SMUG1. Sci Rep 2017; 7(1): 7199.
[52]
Bellacosa A, Drohat AC. Role of base excision repair in maintaining the genetic and epigenetic integrity of CpG sites. DNA Repair (Amst) 2015; 32: 33-42.
[53]
Millar CB, Guy J, Sansom OJ, et al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science 2002; 297(5580): 403-5.
[54]
Wong E, Yang K, Kuraguchi M, et al. Mbd4 inactivation increases right-arrow transition mutations and promotes gastrointestinal tumor formation. Proc Natl Acad Sci USA 2002; 99(23): 14937-42.
[55]
Cortellino S, Turner D, Masciullo V, et al. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc Natl Acad Sci USA 2003; 100(25): 15071-6.
[56]
Cortellino S, Wang C, Wang B, et al. Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol 2009; 325(1): 225-37.
[57]
Grigera F, Wuerffel R, Kenter AL. MBD4 facilitates immunoglobulin class switch recombination. Mol Cell Biol 2017; 37(2)e00316
[58]
Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW. Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III. J Biol Chem 1997; 272(10): 6733-40.
[59]
Dizdaroglu M, Karahalil B, Sentürker S, Buckley TJ, Roldán-Arjona T. Excision of products of oxidative DNA base damage by human NTH1 protein. Biochemistry 1999; 38(1): 243-6.
[60]
Weren RDA, Ligtenberg MJL, Kets CM, et al. A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet 2015; 47(6): 668-71.
[61]
Rivera B, Castellsagué E, Bah I, van Kempen LC, Foulkes WD. Biallelic NTHL1 mutations in a woman with multiple primary tumors. N Engl J Med 2015; 373(20): 1985-6.
[62]
Takao M, Kanno S, Shiromoto T, et al. 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 2002; 21(13): 3486-93.
[63]
Takao M, Kanno S, Kobayashi K, et al. A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue. J Biol Chem 2002; 277(44): 42205-13.
[64]
Ocampo MTA, Chaung W, Marenstein DR, et al. Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity. Mol Cell Biol 2002; 22(17): 6111-21.
[65]
Chan MK, Ocampo-Hafalla MT, Vartanian V, et al. Targeted deletion of the genes encoding NTH1 and NEIL1 DNA N-glycosylases reveals the existence of novel carcinogenic oxidative damage to DNA. DNA Repair (Amst) 2009; 8(7): 786-94.
[66]
Boiteux S, Coste F, Castaing B. Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N-glycosylases. Free Radic Biol Med 2017; 107: 179-201.
[67]
Markkanen E. Not breathing is not an option: How to deal with oxidative DNA damage. DNA Repair (Amst) 2017; 59: 82-105.
[68]
Hung RJ, Hall J, Brennan P, Boffetta P. Genetic polymorphisms in the base excision repair pathway and cancer risk: A HuGE review. Am J Epidemiol 2005; 162(10): 925-42.
[69]
Zhou P-T, Li B, Ji J, Wang M-M, Gao C-F. A systematic review and meta-analysis of the association between OGG1 Ser326Cys polymorphism and cancers. Med Oncol 2015; 32(2): 472.
[70]
Dherin C, Radicella JP, Dizdaroglu M, Boiteux S. Excision of oxidatively damaged DNA bases by the human α-hOgg1 protein and the polymorphic α-hOgg1(Ser326Cys) protein which is frequently found in human populations. Nucleic Acids Res 1999; 27(20): 4001-7.
[71]
Hill JW, Evans MK. Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase. Nucleic Acids Res 2006; 34(5): 1620-32.
[72]
Bravard A, Vacher M, Moritz E, et al. Oxidation status of human OGG1-S326C polymorphic variant determines cellular DNA repair capacity. Cancer Res 2009; 69(8): 3642-9.
[73]
Klungland A, Rosewell I, Hollenbach S, et al. Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci USA 1999; 96(23): 13300-5.
[74]
Minowa O, Arai T, Hirano M, et al. Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice. Proc Natl Acad Sci USA 2000; 97(8): 4156-61.
[75]
Sakumi K, Tominaga Y, Furuichi M, et al. Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption. Cancer Res 2003; 63(5): 902-5.
[76]
Xie Y, Yang H, Cunanan C, et al. Deficiencies in mouse Myh and Ogg1 result in tumor predisposition and G to T mutations in codon 12 of the K-ras oncogene in lung tumors. Cancer Res 2004; 64(9): 3096-102.
[77]
Trapp C, Schwarz M, Epe B. The peroxisome proliferator WY-14,643 promotes hepatocarcinogenesis caused by endogenously generated oxidative DNA base modifications in repair-deficient Csbm/m/Ogg1-/- mice. Cancer Res 2007; 67(11): 5156-61.
[78]
Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y. Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs. EMBO J 2008; 27(2): 421-32.
[79]
Ondovcik SL, Tamblyn L, McPherson JP, Wells PG. Sensitivity to methylmercury toxicity is enhanced in oxoguanine glycosylase 1 knockout murine embryonic fibroblasts and is dependent on cellular proliferation capacity. Toxicol Appl Pharmacol 2013; 270(1): 23-30.
[80]
Tajai P, Fedeles BI, Suriyo T, et al. An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity. Free Radic Biol Med 2018; 116: 64-72.
[81]
Kauppila JHK, Bonekamp NA, Mourier A, et al. Base-excision repair deficiency alone or combined with increased oxidative stress does not increase mtDNA point mutations in mice. Nucleic Acids Res 2018; 46(13): 6642-69.
[82]
Ba X, Boldogh I. 8-Oxoguanine DNA glycosylase 1: Beyond repair of the oxidatively modified base lesions. Redox Biol 2018; 14: 669-78.
[83]
Choi J-Y, Kim H-S, Kang H-K, Lee D-W, Choi E-M, Chung M-H. Thermolabile 8-hydroxyguanine DNA glycosylase with low activity in senescence-accelerated mice due to a single-base mutation. Free Radic Biol Med 1999; 27(7-8): 848-54.
[84]
Mori M, Toyokuni S, Kondo S, et al. Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence. Free Radic Biol Med 2001; 30(10): 1130-6.
[85]
Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biol Chem 2006; 387(4): 373-9.
[86]
Markkanen E, Dorn J, Hübscher U. MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA. Front Genet 2013; 4: 18.
[87]
Al-Tassan N, Chmiel NH, Maynard J, et al. Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. Nat Genet 2002; 30(2): 227-32.
[88]
Sieber OM, Lipton L, Crabtree M, et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 2003; 348(9): 791-9.
[89]
Parker AR, Sieber OM, Shi C, et al. Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair. Carcinogenesis 2005; 26(11): 2010-8.
[90]
Ruggieri V, Pin E, Russo MT, et al. Loss of MUTYH function in human cells leads to accumulation of oxidative damage and genetic instability. Oncogene 2013; 32(38): 4500-8.
[91]
Hirano S, Tominaga Y, Ichinoe A, et al. Mutator phenotype of MUTYH-null mouse embryonic stem cells. J Biol Chem 2003; 278(40): 38121-4.
[92]
Russo MT, De Luca G, Degan P, et al. Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases. Cancer Res 2004; 64(13): 4411-4.
[93]
Sakamoto K, Tominaga Y, Yamauchi K, et al. MUTYH-null mice are susceptible to spontaneous and oxidative stress induced intestinal tumorigenesis. Cancer Res 2007; 67(14): 6599-604.
[94]
Xie Y, Yang H, Miller JH, et al. Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G2/M arrest and multinucleation. Carcinogenesis 2008; 29(4): 722-8.
[95]
Molatore S, Russo MT, D’Agostino VG, et al. MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay. Hum Mutat 2010; 31(2): 159-66.
[96]
Kaina B, Ochs K, Grösch S, et al. BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis. Prog Nucleic Acid Res Mol Biol 2001; 68: 41-54.
[97]
Forbes SA, Beare D, Boutselakis H, et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res 2017; 45(D1): D777-83.
[98]
Hang B, Singer B, Margison GP, Elder RH. Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine. Proc Natl Acad Sci USA 1997; 94(24): 12869-74.
[99]
Engelward BP, Weeda G, Wyatt MD, et al. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase. Proc Natl Acad Sci USA 1997; 94(24): 13087-92.
[100]
Engelward BP, Dreslin A, Christensen J, Huszar D, Kurahara C, Samson L. Repair-deficient 3-methyladenine DNA glycosylase homozygous mutant mouse cells have increased sensitivity to alkylation-induced chromosome damage and cell killing. EMBO J 1996; 15(4): 945-52.
[101]
Roth RB, Samson LD. 3-Methyladenine DNA glycosylase-deficient Aag null mice display unexpected bone marrow alkylation resistance. Cancer Res 2002; 62(3): 656-60.
[102]
Meira LB, Moroski-Erkul CA, Green SL, et al. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice. Proc Natl Acad Sci USA 2009; 106(3): 888-93.
[103]
Margulies CM, Chaim IA, Mazumder A, Criscione J, Samson LD. Alkylation induced cerebellar degeneration dependent on Aag and Parp1 does not occur via previously established cell death mechanisms. PLoS One 2017; 12(9)e0184619
[104]
Grin IR, Zharkov DO. Eukaryotic endonuclease VIII-like proteins: new components of the base excision DNA repair system. Biochemistry (Mosc) 2011; 76(1): 80-93.
[105]
Fleming AM, Burrows CJ. Formation and processing of DNA damage substrates for the hNEIL enzymes. Free Radic Biol Med 2017; 107: 35-52.
[106]
Couvé-Privat S, Macé G, Rosselli F, Saparbaev MK. Psoralen-induced DNA adducts are substrates for the base excision repair pathway in human cells. Nucleic Acids Res 2007; 35(17): 5672-82.
[107]
Talhaoui I, Shafirovich V, Liu Z, et al. Oxidatively generated guanine(C8)–thymine(N3) intrastrand cross-links in double-stranded DNA are repaired by base excision repair pathways. J Biol Chem 2015; 290(23): 14610-7.
[108]
Martin PR, Couvé S, Zutterling C, et al. The human DNA glycosylases NEIL1 and NEIL3 excise psoralen-induced DNA-DNA cross-links in a four-stranded DNA structure. Sci Rep 2017; 7(1): 17438.
[109]
Chaisaingmongkol J, Popanda O, Warta R, et al. Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma. Oncogene 2012; 31(49): 5108-16.
[110]
Do H, Wong NC, Murone C, et al. A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma. Sci Rep 2014; 4: 4186.
[111]
Farkas SA, Vymetalkova V, Vodickova L, Vodicka P, Nilsson TK. DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/β-catenin signaling pathway genes. Epigenomics 2014; 6(2): 179-91.
[112]
Vartanian V, Lowell B, Minko IG, et al. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc Natl Acad Sci USA 2006; 103(6): 1864-9.
[113]
Sampath H, Batra AK, Vartanian V, et al. Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice. Am J Physiol Endocrinol Metab 2011; 300(4): E724-34.
[114]
Jaruga P, Xiao Y, Vartanian V, Lloyd RS, Dizdaroglu M. Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5′R)- and (5′S)-8,5′-cyclo-2′-deoxyadenosines. Biochemistry 2010; 49(6): 1053-5.
[115]
Vartanian V, Minko IG, Chawanthayatham S, et al. NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice. Proc Natl Acad Sci USA 2017; 114(16): 4207-12.
[116]
Mori H, Ouchida R, Hijikata A, et al. Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion. DNA Repair (Amst) 2009; 8(11): 1328-32.
[117]
Canugovi C, Yoon JS, Feldman NH, Croteau DL, Mattson MP, Bohr VA. Endonuclease VIII-like 1 (NEIL1) promotes short-term spatial memory retention and protects from ischemic stroke-induced brain dysfunction and death in mice. Proc Natl Acad Sci USA 2012; 109(37): 14948-53.
[118]
Canugovi C, Misiak M, Scheibye-Knudsen M, Croteau DL, Mattson MP, Bohr VA. Loss of NEIL1 causes defects in olfactory function in mice. Neurobiol Aging 2015; 36(2): 1007-12.
[119]
Rosenquist TA, Zaika E, Fernandes AS, Zharkov DO, Miller H, Grollman AP. The novel DNA glycosylase, NEIL1, protects mammalian cells from radiation-mediated cell death. DNA Repair (Amst) 2003; 2(5): 581-91.
[120]
Carmell MA, Zhang L, Conklin DS, Hannon GJ, Rosenquist TA. Germline transmission of RNAi in mice. Nat Struct Biol 2003; 10(2): 91-2.
[121]
Zou X, Owusu M, Harris R, Jackson SP, Loizou JI, Nik-Zainal S. Validating the concept of mutational signatures with isogenic cell models. Nat Commun 2018; 9(1): 1744.
[122]
Dou H, Mitra S, Hazra TK. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J Biol Chem 2003; 278(50): 49679-84.
[123]
Chakraborty A, Wakamiya M, Venkova-Canova T, et al. Neil2-null mice accumulate oxidized DNA bases in the transcriptionally active sequences of the genome and are susceptible to innate inflammation. J Biol Chem 2015; 290(41): 24636-48.
[124]
Liu M, Doublié S, Wallace SS. Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage. Mutat Res 2013; 743-744: 4-11.
[125]
Massaad MJ, Zhou J, Tsuchimoto D, et al. Deficiency of base excision repair enzyme NEIL3 drives increased predisposition to autoimmunity. J Clin Invest 2016; 126(11): 4219-36.
[126]
Torisu K, Tsuchimoto D, Ohnishi Y, Nakabeppu Y. Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease VIII-like protein. J Biochem 2005; 138(6): 763-72.
[127]
Sejersted Y, Hildrestrand GA, Kunke D, et al. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. Proc Natl Acad Sci USA 2011; 108(46): 18802-7.
[128]
Regnell CE, Hildrestrand GA, Sejersted Y, et al. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Cell Rep 2012; 2(3): 503-10.
[129]
Rolseth V, Krokeide SZ, Kunke D, et al. Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress. Biochim Biophys Acta 2013; 1833(5): 1157-64.
[130]
Demple B, Sung J-S. Molecular and biological roles of Ape1 protein in mammalian base excision repair. DNA Repair (Amst) 2005; 4(12): 1442-9.
[131]
Xanthoudakis S, Miao G, Wang F, Pan Y-CE, Curran T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J 1992; 11(9): 3323-35.
[133]
Georgiadis MM, Luo M, Gaur RK, Delaplane S, Li X, Kelley MR. Evolution of the redox function in mammalian apurinic/ apyrimidinic endonuclease. Mutat Res 2008; 643(1-2): 54-63.
[134]
Xanthoudakis S, Smeyne RJ, Wallace JD, Curran T. The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci USA 1996; 93(17): 8919-23.
[135]
Ludwig DL, MacInnes MA, Takiguchi Y, et al. A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity. Mutat Res 1998; 409(1): 17-29.
[136]
Meira LB, Devaraj S, Kisby GE, et al. Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Res 2001; 61(14): 5552-7.
[137]
Wang Y, Shupenko CC, Melo LF, Strauss PR. DNA repair protein involved in heart and blood development. Mol Cell Biol 2006; 26(23): 9083-93.
[138]
Masani S, Han L, Yu K. Apurinic/apyrimidinic endonuclease 1 is the essential nuclease during immunoglobulin class switch recombination. Mol Cell Biol 2013; 33(7): 1468-73.
[139]
Chen T, Liu C, Lu H, et al. The expression of APE1 in triple-negative breast cancer and its effect on drug sensitivity of olaparib. Tumour Biol 2017; 39(10)1010428317713390
[140]
Izumi T, Brown DB, Naidu CV, et al. Two essential but distinct functions of the mammalian abasic endonuclease. Proc Natl Acad Sci USA 2005; 102(16): 5739-43.
[141]
Stetler RA, Gao Y, Leak RK, et al. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury. Proc Natl Acad Sci USA 2016; 113(25): E3558-67.
[142]
Ordway JM, Eberhart D, Curran T. Cysteine 64 of Ref-1 is not essential for redox regulation of AP-1 DNA binding. Mol Cell Biol 2003; 23(12): 4257-66.
[143]
Raffoul JJ, Cabelof DC, Nakamura J, Meira LB, Friedberg EC, Heydari AR. Apurinic/apyrimidinic endonuclease (APE/REF-1) haploinsufficient mice display tissue-specific differences in DNA polymerase β-dependent base excision repair. J Biol Chem 2004; 279(18): 18425-33.
[144]
Huamani J, McMahan CA, Herbert DC, et al. Spontaneous mutagenesis is enhanced in Apex heterozygous mice. Mol Cell Biol 2004; 24(18): 8145-53.
[145]
Unnikrishnan A, Raffoul JJ, Patel HV, et al. Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice. Free Radic Biol Med 2009; 46(11): 1488-99.
[146]
Vogel KS, Perez M, Momand JR, et al. Age-related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice. Mol Reprod Dev 2011; 78(12): 906-19.
[147]
Ballista-Hernández J, Martínez-Ferrer M, Vélez R, et al. Mitochondrial DNA integrity is maintained by APE1 in carcinogen-induced colorectal cancer. Mol Cancer Res 2017; 15(7): 831-41.
[148]
Meira LB, Cheo DL, Hammer RE, Burns DK, Reis A, Friedberg EC. Genetic interaction between HAP1/REF-1 and p53. Nat Genet 1997; 17(2): 145.
[149]
Cheo DL, Meira LB, Burns DK, Reis AM, Issac T, Friedberg EC. Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors. Cancer Res 2000; 60(6): 1580-4.
[150]
Jeon BH, Gupta G, Park YC, et al. Apurinic/apyrimidinic endonuclease 1 regulates endothelial NO production and vascular tone. Circ Res 2004; 95(9): 902-10.
[151]
Basi DL, Adhikari N, Mariash A, et al. Femoral artery neointimal hyperplasia is reduced after wire injury in Ref-1+/- mice. Am J Physiol Heart Circ Physiol 2007; 292(1): H516-21.
[152]
Jung S-B, Kim C-S, Kim Y-R, et al. Redox factor-1 activates endothelial SIRTUIN1 through reduction of conserved cysteine sulfhydryls in its deacetylase domain. PLoS One 2013; 8(6)e65415
[153]
Silber JR, Bobola MS, Blank A, et al. The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res 2002; 8(9): 3008-18.
[154]
Wang D, Luo M, Kelley MR. Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition. Mol Cancer Ther 2004; 3(6): 679-86.
[155]
Fung H, Demple B. Distinct roles of Ape1 protein in the repair of DNA damage induced by ionizing radiation or bleomycin. J Biol Chem 2011; 286(7): 4968-77.
[156]
Naidu MD, Mason JM, Pica RV, Fung H, Peña LA. Radiation resistance in glioma cells determined by DNA damage repair activity of Ape1/Ref-1. J Radiat Res (Tokyo) 2010; 51(4): 393-404.
[157]
Beard WA, Wilson SH. Structure and mechanism of DNA polymerase β. Chem Rev 2006; 106(2): 361-82.
[158]
Sobol RW, Prasad R, Evenski A, et al. The lyase activity of the DNA repair protein β-polymerase protects from DNA-damage-induced cytotoxicity. Nature 2000; 405(6788): 807-10.
[159]
Starcevic D, Dalal S, Sweasy JB. Is there a link between DNA polymerase β and cancer? Cell Cycle 2004; 3(8): 998-1001.
[160]
Chan KKL, Zhang Q-M, Dianov GL. Base excision repair fidelity in normal and cancer cells. Mutagenesis 2006; 21(3): 173-8.
[161]
Senejani AG, Dalal S, Liu Y, et al. Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates. Proc Natl Acad Sci USA 2012; 109(17): 6632-7.
[162]
Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. Deletion of a DNA polymerase β gene segment in T cells using cell type-specific gene targeting. Science 1994; 265(5168): 103-6.
[163]
Sobol RW, Horton JK, Kühn R, et al. Requirement of mammalian DNA polymerase-β in base-excision repair. Nature 1996; 379(6561): 183-6.
[164]
Sugo N, Aratani Y, Nagashima Y, Kubota Y, Koyama H. Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase β. EMBO J 2000; 19(6): 1397-404.
[165]
Sobol RW, Kartalou M, Almeida KH, et al. Base excision repair intermediates induce p53-independent cytotoxic and genotoxic responses. J Biol Chem 2003; 278(41): 39951-9.
[166]
Tano K, Nakamura J, Asagoshi K, et al. Interplay between DNA polymerases β and λ in repair of oxidation DNA damage in chicken DT40 cells. DNA Repair (Amst) 2007; 6(6): 869-75.
[167]
Ridpath JR, Takeda S, Swenberg JA, Nakamura J. Convenient, multi-well plate-based DNA damage response analysis using DT40 mutants is applicable to a high-throughput genotoxicity assay with characterization of modes of action. Environ Mol Mutagen 2011; 52(2): 153-60.
[168]
García-Díaz M, Bebenek K, Kunkel TA, Blanco L. Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase λ: A possible role in base excision repair. J Biol Chem 2001; 276(37): 34659-63.
[169]
Bebenek K, Tissier A, Frank EG, et al. 5′-Deoxyribose phosphate lyase activity of human DNA polymerase ι in vitro. Science 2001; 291(5511): 2156-9.
[170]
Miropolskaya N, Petushkov I, Kulbachinskiy A, Makarova AV. Identification of amino acid residues involved in the dRP-lyase activity of human Pol ι. Sci Rep 2017; 7(1): 10194.
[171]
Prasad R, Poltoratsky V, Hou EW, Wilson SH. Rev1 is a base excision repair enzyme with 5′-deoxyribose phosphate lyase activity. Nucleic Acids Res 2016; 44(22): 10824-33.
[172]
Prasad R, Longley MJ, Sharief FS, Hou EW, Copeland WC, Wilson SH. Human DNA polymerase θ possesses 5′-dRP lyase activity and functions in single-nucleotide base excision repair in vitro. Nucleic Acids Res 2009; 37(6): 1868-77.
[173]
Moon AF, Garcia-Diaz M, Batra VK, et al. The X family portrait: structural insights into biological functions of X family polymerases. DNA Repair (Amst) 2007; 6(12): 1709-25.
[174]
van Loon B, Hübscher U, Maga G. Living on the edge: DNA polymerase lambda between genome stability and mutagenesis. Chem Res Toxicol 2017; 30(11): 1936-41.
[175]
Braithwaite EK, Kedar PS, Lan L, et al. DNA polymerase λ protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair. J Biol Chem 2005; 280(36): 31641-7.
[176]
Braithwaite EK, Kedar PS, Stumpo DJ, et al. DNA polymerases β and λ mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts. PLoS One 2010; 5(8)e12229
[177]
Crespan E, Hübscher U, Maga G. Error-free bypass of 2-hydroxyadenine by human DNA polymerase λ with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contexts. Nucleic Acids Res 2007; 35(15): 5173-81.
[178]
Maga G, Villani G, Crespan E, et al. 8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteins. Nature 2007; 447(7144): 606-8.
[179]
van Loon B, Hübscher U. An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase λ. Proc Natl Acad Sci USA 2009; 106(43): 18201-6.
[180]
Bertocci B, De Smet A, Flatter E, et al. Cutting edge: DNA polymerases μ and λ are dispensable for Ig gene hypermutation. J Immunol 2002; 168(8): 3702-6.
[181]
Vermeulen C, Bertocci B, Begg AC, Vens C. Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells. Radiat Res 2007; 168(6): 683-8.
[182]
Maga G, Crespan E, Markkanen E, et al. DNA polymerase δ-interacting protein 2 is a processivity factor for DNA polymerase λ during 8-oxo-7,8-dihydroguanine bypass. Proc Natl Acad Sci USA 2013; 110(47): 18850-5.
[183]
Kanagaraj R, Parasuraman P, Mihaljevic B, et al. Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage. Nucleic Acids Res 2012; 40(17): 8449-59.
[184]
Makarova AV, Kulbachinskiy AV. Structure of human DNA polymerase iota and the mechanism of DNA synthesis. Biochemistry (Mosc) 2012; 77(6): 547-61.
[185]
Prasad R, Bebenek K, Hou E, et al. Localization of the deoxyribose phosphate lyase active site in human DNA polymerase ι by controlled proteolysis. J Biol Chem 2003; 278(32): 29649-54.
[186]
Petta TB, Nakajima S, Zlatanou A, et al. Human DNA polymerase iota protects cells against oxidative stress. EMBO J 2008; 27(21): 2883-95.
[187]
McDonald JP, Frank EG, Plosky BS, et al. 129-derived strains of mice are deficient in DNA polymerase ι and have normal immunoglobulin hypermutation. J Exp Med 2003; 198(4): 635-43.
[188]
Kazachenko KY, Miropolskaya NA, Gening LV, Tarantul VZ, Makarova AV. Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro. DNA Repair (Amst) 2017; 50: 77-82.
[189]
Frank EG, McDonald JP, Yang W, Woodgate R. Mouse DNA polymerase ι lacking the forty-two amino acids encoded by exon-2 is catalytically inactive in vitro. DNA Repair (Amst) 2017; 50: 71-6.
[190]
Dumstorf CA, Clark AB, Lin Q, et al. Participation of mouse DNA polymerase ι in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer. Proc Natl Acad Sci USA 2006; 103(48): 18083-8.
[191]
Ohkumo T, Kondo Y, Yokoi M, et al. UV-B radiation induces epithelial tumors in mice lacking DNA polymerase η and mesenchymal tumors in mice deficient for DNA polymerase ι. Mol Cell Biol 2006; 26(20): 7696-706.
[192]
Faili A, Aoufouchi S, Flatter E, Guéranger Q, Reynaud C-A, Weill J-C. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature 2002; 419(6910): 944-7.
[193]
Aoufouchi S, De Smet A, Delbos F, et al. 129-Derived mouse strains express an unstable but catalytically active DNA polymerase iota variant. Mol Cell Biol 2015; 35(17): 3059-70.
[194]
Gueranger Q, Stary A, Aoufouchi S, et al. Role of DNA polymerases η, ι and ζ in UV resistance and UV-induced mutagenesis in a human cell line. DNA Repair (Amst) 2008; 7(9): 1551-62.
[195]
Masuda Y, Takahashi M, Fukuda S, Sumii M, Kamiya K. Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein. J Biol Chem 2002; 277(4): 3040-6.
[196]
Zhang Y, Wu X, Rechkoblit O, Geacintov NE, Taylor J-S, Wang Z. Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion. Nucleic Acids Res 2002; 30(7): 1630-8.
[198]
Ross A-L, Sale JE. The catalytic activity of REV1 is employed during immunoglobulin gene diversification in DT40. Mol Immunol 2006; 43(10): 1587-94.
[199]
Jansen JG, Langerak P, Tsaalbi-Shtylik A, van den Berk P, Jacobs H, de Wind N. Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice. J Exp Med 2006; 203(2): 319-23.
[200]
Masuda K, Ouchida R, Li Y, Gao X, Mori H, Wang J-Y. A critical role for REV1 in regulating the induction of C:G transitions and A:T mutations during Ig gene hypermutation. J Immunol 2009; 183(3): 1846-50.
[201]
Kano C, Hanaoka F, Wang J-Y. Analysis of mice deficient in both REV1 catalytic activity and POLH reveals an unexpected role for POLH in the generation of C to G and G to C transversions during Ig gene hypermutation. Int Immunol 2012; 24(3): 169-74.
[202]
Wood RD, Doublié S. DNA polymerase θ (POLQ), double-strand break repair, and cancer. DNA Repair (Amst) 2016; 44: 22-32.
[203]
Goff JP, Shields DS, Seki M, et al. Lack of DNA polymerase θ (POLQ) radiosensitizes bone marrow stromal cells in vitro and increases reticulocyte micronuclei after total-body irradiation. Radiat Res 2009; 172(2): 165-74.
[204]
Li Y, Gao X, Wang J-Y. Comparison of two POLQ mutants reveals that a polymerase-inactive POLQ retains significant function in tolerance to etoposide and γ-irradiation in mouse B cells. Genes Cells 2011; 16(9): 973-83.
[205]
Yousefzadeh MJ, Wyatt DW, Takata K, et al. Mechanism of suppression of chromosomal instability by DNA polymerase POLQ. PLoS Genet 2014; 10(10)e1004654
[206]
Zan H, Shima N, Xu Z, et al. The translesion DNA polymerase θ plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J 2005; 24(21): 3757-69.
[207]
Masuda K, Ouchida R, Takeuchi A, et al. DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes. Proc Natl Acad Sci USA 2005; 102(39): 13986-91.
[208]
Ukai A, Maruyama T, Mochizuki S, et al. Role of DNA polymerase θ in tolerance of endogenous and exogenous DNA damage in mouse B cells. Genes Cells 2006; 11(2): 111-21.
[209]
Yoshimura M, Kohzaki M, Nakamura J, et al. Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage. Mol Cell 2006; 24(1): 115-25.
[210]
Harrington JJ, Lieber MR. The characterization of a mammalian DNA structure-specific endonuclease. EMBO J 1994; 13(5): 1235-46.
[211]
Murante RS, Huang L, Turchi JJ, Bambara RA. The calf 5′- to 3′-exonuclease is also an endonuclease with both activities dependent on primers annealed upstream of the point of cleavage. J Biol Chem 1994; 269(2): 1191-6.
[212]
Li X, Li J, Harrington J, Lieber MR, Burgers PMJ. Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen. J Biol Chem 1995; 270(38): 22109-12.
[213]
Bornarth CJ, Ranalli TA, Henricksen LA, Wahl AF, Bambara RA. Effect of flap modifications on human FEN1 cleavage. Biochemistry 1999; 38(40): 13347-54.
[214]
Liu Y, Kao H-I, Bambara RA. Flap endonuclease 1: A central component of DNA metabolism. Annu Rev Biochem 2004; 73: 589-615.
[215]
Tomlinson CG, Atack JM, Chapados B, Tainer JA, Grasby JA. Substrate recognition and catalysis by flap endonucleases and related enzymes. Biochem Soc Trans 2010; 38(2): 433-7.
[216]
Zheng L, Dai H, Zhou M, et al. Fen1 mutations result in autoimmunity, chronic inflammation and cancers. Nat Med 2007; 13(7): 812-9.
[217]
Kucherlapati M, Yang K, Kuraguchi M, et al. Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression. Proc Natl Acad Sci USA 2002; 99(15): 9924-9.
[218]
Larsen E, Gran C, Saether BE, Seeberg E, Klungland A. Proliferation failure and gamma radiation sensitivity of Fen1 null mutant mice at the blastocyst stage. Mol Cell Biol 2003; 23(15): 5346-53.
[219]
Xu H, Zheng L, Dai H, Zhou M, Hua Y, Shen B. Chemical-induced cancer incidence and underlying mechanisms in Fen1 mutant mice. Oncogene 2011; 30(9): 1072-81.
[220]
Shibata Y, Nakamura T. Defective flap endonuclease 1 activity in mammalian cells is associated with impaired DNA repair and prolonged S phase delay. J Biol Chem 2002; 277(1): 746-54.
[221]
Sun H, He L, Wu H, et al. The FEN1 L209P mutation interferes with long-patch base excision repair and induces cellular transformation. Oncogene 2017; 36(2): 194-207.
[222]
Matsuzaki Y, Adachi N, Koyama H. Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2. Nucleic Acids Res 2002; 30(14): 3273-7.
[223]
Urbanucci A, Sahu B, Seppälä J, et al. Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer. Oncogene 2012; 31(17): 2153-63.
[224]
Nikolova T, Christmann M, Kaina B. FEN1 is overexpressed in testis, lung and brain tumors. Anticancer Res 2009; 29(7): 2453-9.
[225]
Levin DS, Bai W, Yao N, O’Donnell M, Tomkinson AE. An interaction between DNA ligase I and proliferating cell nuclear antigen: implications for Okazaki fragment synthesis and joining. Proc Natl Acad Sci USA 1997; 94(24): 12863-8.
[226]
Levin DS, McKenna AE, Motycka TA, Matsumoto Y, Tomkinson AE. Interaction between PCNA and DNA ligase I is critical for joining of Okazaki fragments and long-patch base-excision repair. Curr Biol 2000; 10(15): 919-22.
[227]
Ellenberger T, Tomkinson AE. Eukaryotic DNA ligases: structural and functional insights. Annu Rev Biochem 2008; 77: 313-38.
[228]
Tomkinson AE, Chen L, Dong Z, et al. Completion of base excision repair by mammalian DNA ligases. Prog Nucleic Acid Res Mol Biol 2001; 68: 151-64.
[229]
Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T. Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. Cell 1992; 69(3): 495-503.
[230]
Webster ADB, Barnes DE, Arlett CF, Lehmann AR, Lindahl T. Growth retardation and immunodeficiency in a patient with mutations in the DNA ligase I gene. Lancet 1992; 339(8808): 1508-9.
[231]
Teo IA, Arlett CF, Harcourt SA, Priestley A, Broughton BC. Multiple hypersensitivity to mutagens in a cell strain (46BR) derived from a patient with immuno-deficiencies. Mutat Res 1983; 107(2): 371-86.
[232]
Teo IA, Broughton BC, Day RS, et al. A biochemical defect in the repair of alkylated DNA in cells from an immunodeficient patient (46BR). Carcinogenesis 1983; 4(5): 559-64.
[233]
Squires S, Johnson RTUv. induces long-lived DNA breaks in Cockayne’s syndrome and cells from an immunodeficient individual (46BR): defects and disturbance in post incision steps of excision repair. Carcinogenesis 1983; 4(5): 565-72.
[234]
Henderson LM, Arlett CF, Harcourt SA, Lehmann AR, Broughton BC. Cells from an immunodeficient patient (46BR) with a defect in DNA ligation are hypomutable but hypersensitive to the induction of sister chromatid exchanges. Proc Natl Acad Sci USA 1985; 82(7): 2044-8.
[235]
Lehmann AR, Willis AE, Broughton BC, et al. Relation between the human fibroblast strain 46BR and cell lines representative of Bloom’s syndrome. Cancer Res 1988; 48(22): 6343-7.
[236]
Somia NV, Jessop JK, Melton DW. Phenotypic correction of a human cell line (46BR) with aberrant DNA ligase I activity. Mutat Res 1993; 294(1): 51-8.
[237]
Moser J, Kool H, Giakzidis I, Caldecott K, Mullenders LHF, Fousteri MI. Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III α in a cell-cycle-specific manner. Mol Cell 2007; 27(2): 311-23.
[238]
Soza S, Leva V, Vago R, et al. DNA ligase I deficiency leads to replication-dependent DNA damage and impacts cell morphology without blocking cell cycle progression. Mol Cell Biol 2009; 29(8): 2032-41.
[239]
Giuliano S, Iadarola P, Leva V, et al. An insight into the abundant proteome of 46BR.1G1 fibroblasts deficient of DNA ligase I. Electrophoresis 2012; 33(2): 307-15.
[240]
Arlett CF, Priestley A. Defective recovery from potentially lethal damage in some human fibroblast cell strains. Int J Radiat Biol Relat Stud Phys Chem Med 1983; 43(2): 157-67.
[241]
Fertil B, Deschavanne PJ, Debieu D, Malaise EP. Correlation between PLD repair capacity and the survival curve of human fibroblasts in exponential growth phase: Analysis in terms of several parameters. Radiat Res 1988; 116(1): 74-88.
[242]
Wilson PF, Nham PB, Urbin SS, Hinz JM, Jones IM, Thompson LH. Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation. Mutat Res 2010; 683(1-2): 91-7.
[243]
Arlett CF, Green MHL, Priestley A, Harcourt SA, Mayne LV. Comparative human cellular radiosensitivity: I. The effect of SV40 transformation and immortalisation on the gamma-irradiation survival of skin derived fibroblasts from normal individuals and from ataxia-telangiectasia patients and heterozygotes. Int J Radiat Biol 1988; 54(6): 911-28.
[244]
López Castel A, Tomkinson AE, Pearson CE. CTG/CAG repeat instability is modulated by the levels of human DNA ligase I and its interaction with proliferating cell nuclear antigen: A distinction between replication and slipped-DNA repair. J Biol Chem 2009; 284(39): 26631-45.
[245]
Harrison C, Ketchen A-M, Redhead NJ, O’Sullivan MJ, Melton DW. Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene. Cancer Res 2002; 62(14): 4065-74.
[246]
Bentley D, Selfridge J, Millar JK, et al. DNA ligase I is required for fetal liver erythropoiesis but is not essential for mammalian cell viability. Nat Genet 1996; 13(4): 489-91.
[247]
Bentley DJ, Harrison C, Ketchen A-M, et al. DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability. J Cell Sci 2002; 115(Pt 7): 1551-61.
[248]
Petrini JHJ, Xiao Y, Weaver DT. DNA ligase I mediates essential functions in mammalian cells. Mol Cell Biol 1995; 15(8): 4303-8.
[249]
Han L, Masani S, Hsieh CL, Yu K. DNA ligase I is not essential for mammalian cell viability. Cell Rep 2014; 7(2): 316-20.
[250]
Arakawa H, Bednar T, Wang M, et al. Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells. Nucleic Acids Res 2012; 40(6): 2599-610.
[251]
Le Chalony C, Hoffschir F, Gauthier LR, et al. Partial complementation of a DNA ligase I deficiency by DNA ligase III and its impact on cell survival and telomere stability in mammalian cells. Cell Mol Life Sci 2012; 69(17): 2933-49.
[252]
Mackey ZB, Ramos W, Levin DS, Walter CA, McCarrey JR, Tomkinson AE. An alternative splicing event which occurs in mouse pachytene spermatocytes generates a form of DNA ligase III with distinct biochemical properties that may function in meiotic recombination. Mol Cell Biol 1997; 17(2): 989-98.
[253]
Perez-Jannotti RM, Klein SM, Bogenhagen DF. Two forms of mitochondrial DNA ligase III are produced in Xenopus laevis oocytes. J Biol Chem 2001; 276(52): 48978-87.
[254]
Tomkinson AE, Sallmyr A. Structure and function of the DNA ligases encoded by the mammalian LIG3 gene. Gene 2013; 531(2): 150-7.
[255]
Lakshmipathy U, Campbell C. The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol Cell Biol 1999; 19(5): 3869-76.
[256]
Puebla-Osorio N, Lacey DB, Alt FW, Zhu C. Early embryonic lethality due to targeted inactivation of DNA ligase III. Mol Cell Biol 2006; 26(10): 3935-41.
[257]
Simsek D, Furda A, Gao Y, et al. Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair. Nature 2011; 471(7337): 245-8.
[258]
Boboila C, Oksenych V, Gostissa M, et al. Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1). Proc Natl Acad Sci USA 2012; 109(7): 2473-8.
[259]
Gao Y, Katyal S, Lee Y, et al. DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair. Nature 2011; 471(7337): 240-4.
[261]
Almeida KH, Sobol RW. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair (Amst) 2007; 6(6): 695-711.
[262]
London RE. The structural basis of XRCC1-mediated DNA repair. DNA Repair (Amst) 2015; 30: 90-103.
[263]
Thompson LH, Rubin JS, Cleaver JE, Whitmore GF, Brookman K. A screening method for isolating DNA repair-deficient mutants of CHO cells. Somatic Cell Genet 1980; 6(3): 391-405.
[264]
Thompson LH, Brookman KW, Dillehay LE, et al. A CHO-cell strain having hypersensitivity to mutagens, a defect in DNA strand-break repair, and an extraordinary baseline frequency of sister-chromatid exchange. Mutat Res 1982; 95(2-3): 427-40.
[265]
Thompson LH, Brookman KW, Jones NJ, Allen SA, Carrano AV. Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Mol Cell Biol 1990; 10(12): 6160-71.
[266]
Caldecott KW, Tucker JD, Thompson LH. Construction of human XRCC1 minigenes that fully correct the CHO DNA repair mutant EM9. Nucleic Acids Res 1992; 20(17): 4575-9.
[267]
Zdzienicka MZ, van der Schans GP, Natarajan AT, Thompson LH, Neuteboom I, Simons JWIM. A Chinese hamster ovary cell mutant (EM-C11) with sensitivity to simple alkylating agents and a very high level of sister chromatid exchanges. Mutagenesis 1992; 7(4): 265-9.
[268]
Hoch NC, Hanzlikova H, Rulten SL, et al. XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature 2017; 541(7635): 87-91.
[269]
Tebbs RS, Flannery ML, Meneses JJ, et al. Requirement for the Xrcc1 DNA base excision repair gene during early mouse development. Dev Biol 1999; 208(2): 513-29.
[270]
Tebbs RS, Thompson LH, Cleaver JE. Rescue of Xrcc1 knockout mouse embryo lethality by transgene-complementation. DNA Repair (Amst) 2003; 2(12): 1405-17.
[271]
Lee Y, Katyal S, Li Y, et al. The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1. Nat Neurosci 2009; 12(8): 973-80.
[272]
Hottiger MO. Nuclear ADP-ribosylation and its role in chromatin plasticity, cell differentiation, and epigenetics. Annu Rev Biochem 2015; 84: 227-63.
[273]
Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol 2017; 18(10): 610-21.
[274]
Byers LA, Wang J, Nilsson MB, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov 2012; 2(9): 798-811.
[275]
Wang Z-Q, Auer B, Stingl L, et al. Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev 1995; 9(5): 509-20.
[276]
de Murcia JM, Niedergang C, Trucco C, et al. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci USA 1997; 94(14): 7303-7.
[277]
Masutani M, Suzuki H, Kamada N, et al. Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci USA 1999; 96(5): 2301-4.
[278]
Ménisser-de Murcia J, Mark M, Wendling O, Wynshaw-Boris A, de Murcia G. Early embryonic lethality in PARP-1 Atm double-mutant mice suggests a functional synergy in cell proliferation during development. Mol Cell Biol 2001; 21(5): 1828-32.
[279]
Henrie MS, Kurimasa A, Burma S, et al. Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis. DNA Repair (Amst) 2003; 2(2): 151-8.
[280]
Ménissier de Murcia J, Ricoul M, Tartier L, et al. Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse. EMBO J 2003; 22(9): 2255-63.
[281]
Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434(7035): 913-7.
[282]
Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434(7035): 917-21.
[283]
Maya-Mendoza A, Moudry P, Merchut-Maya JM, Lee M, Strauss R, Bartek J. High speed of fork progression induces DNA replication stress and genomic instability. Nature 2018; 559(7713): 279-84.
[284]
Zimmermann M, Murina O, Reijns MAM, et al. CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. Nature 2018; 559(7713): 285-9.
[285]
Aredia F, Scovassi AI. Poly(ADP-ribose): A signaling molecule in different paradigms of cell death. Biochem Pharmacol 2014; 92(1): 157-63.
[286]
Lupo B, Trusolino L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited. Biochim Biophys Acta 2014; 1846(1): 201-15.
[287]
Cimino MC. Comparative overview of current international strategies and guidelines for genetic toxicology testing for regulatory purposes. Environ Mol Mutagen 2006; 47(5): 362-90.
[288]
Kirkland D, Speit G. Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens III. Appropriate follow-up testing in vivo. Mutat Res 2008; 654(2): 114-32.
[289]
Hendriks G, van de Water B, Schoonen W, Vrieling H. Cellular-signaling pathways unveil the carcinogenic potential of chemicals. J Appl Toxicol 2013; 33(6): 399-409.
[290]
Evans TJ, Yamamoto KN, Hirota K, Takeda S. Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity. DNA Repair (Amst) 2010; 9(12): 1292-8.
[291]
Kang SH, Kwon JY, Lee JK, Seo YR. Recent advances in in vivo genotoxicity testing: prediction of carcinogenic potential using comet and micronucleus assay in animal models. J Cancer Prev 2013; 18(4): 277-88.
[292]
Hoy CA, Salazar EP, Thompson LH. Rapid detection of DNA-damaging agents using repair-deficient CHO cells. Mutat Res 1984; 130(5): 321-32.
[293]
Johansson F, Allkvist A, Erixon K, et al. Screening for genotoxicity using the DRAG assay: investigation of halogenated environmental contaminants. Mutat Res 2004; 563(1): 35-47.
[294]
Saha LK, Kim S, Kang H, et al. Differential micronucleus frequency in isogenic human cells deficient in DNA repair pathways is a valuable indicator for evaluating genotoxic agents and their genotoxic mechanisms. Environ Mol Mutagen 2018; 59(6): 529-38.
[295]
Sykora P, Witt KL, Revanna P, et al. Next generation high throughput DNA damage detection platform for genotoxic compound screening. Sci Rep 2018; 8(1): 2771.
[296]
Lee S, Liu X, Takeda S, Choi K. Genotoxic potentials and related mechanisms of bisphenol A and other bisphenol compounds: A comparison study employing chicken DT40 cells. Chemosphere 2013; 93(2): 434-40.
[297]
Liu X, Lee J, Ji K, Takeda S, Choi K. Potentials and mechanisms of genotoxicity of six pharmaceuticals frequently detected in freshwater environment. Toxicol Lett 2012; 211(1): 70-6.
[298]
Smith S, Fox J, Mejia M, et al. Histone deacetylase inhibitors selectively target homology dependent DNA repair defective cells and elevate non-homologous endjoining activity. PLoS One 2014; 9(1)e87203
[299]
Ji K, Kogame T, Choi K, et al. A novel approach using DNA-repair-deficient chicken DT40 cell lines for screening and characterizing the genotoxicity of environmental contaminants. Environ Health Perspect 2009; 117(11): 1737-44.
[300]
Hu J, Nakamura J, Richardson SD, Aitken MD. Evaluating the effects of bioremediation on genotoxicity of polycyclic aromatic hydrocarbon-contaminated soil using genetically engineered, higher eukaryotic cell lines. Environ Sci Technol 2012; 46(8): 4607-13.
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