Redox reactions are known to regulate many important cellular processes. In this review, we focus on the role of redox regulation in DNA repair both in direct regulation of specific DNA repair proteins as well as indirect transcriptional regulation. A key player in the redox regulation of DNA repair is the base excision repair enzyme apurinic/apyrimidinic endonuclease 1 (APE1) in its role as a redox factor. APE1 is reduced by the general redox factor thioredoxin, and in turn reduces several important transcription factors that regulate expression of DNA repair proteins. Finally, we consider the potential for chemotherapeutic development through the modulation of APE1's redox activity and its impact on DNA repair. Antioxid. Redox Signal. 12, 1247–1269.
AbateC, LukD, GentzR, RauscherFJ 3rd, CurranT. Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly. Proc Natl Acad Sci U S A, 87:1032–1036. 1990.
2.
AbateC, PatelL, RauscherFJ3rd, CurranT. Redox regulation of fos and jun DNA-binding activity in vitro. Science, 249:1157–1161.
3.
AdimoolamS, FordJM. p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene. Proc Natl Acad Sci U S A, 99:12985–12990. 2002.
4.
AiyerHS, KichambareS, GuptaRC. Prevention of oxidative DNA damage by bioactive berry components. Nutr Cancer, 60,suppl 1:36–42. 2008.
5.
AiyerHS, SrinivasanC, GuptaRC. Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats. Nutr Cancer, 60:227–234. 2008
6.
AkamatsuY, OhnoT, HirotaK, KagoshimaH, YodoiJ, ShigesadaK. Redox regulation of the DNA binding activity in transcription factor PEBP2: the roles of two conserved cysteine residues. J Biol Chem, 272:14497–14500. 1997.
7.
AkterinS, CowburnRF, Miranda-VizueteA, JimenezA, BogdanovicN, WinbladB, Cedazo-MinguezA. Involvement of glutaredoxin-1 and thioredoxin-1 in beta-amyloid toxicity and Alzheimer's disease. Cell Death Differ, 13:1454–1465. 2006.
8.
AltieriF, GrilloC, MaceroniM, ChichiarelliS. DNA damage and repair: from molecular mechanisms to health implications. Antioxid Redox Signal, 10:891–937. 2008.
9.
AngkeowP, DeshpandeSS, QiB, LiuYX, ParkYC, JeonBH, OzakiM, IraniK. Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis. Cell Death Differ, 9:717–725. 2002.
10.
Arias-LopezC, Lazaro-TruebaI, KerrP, LordCJ, DexterT, IravaniM, AshworthA, SilvaA. p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene. EMBO Rep, 7:219–224. 2006.
11.
ArnerES, HolmgrenA. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem, 267:6102–6109. 2000.
12.
ArnerES, HolmgrenA. The thioredoxin system in cancer. Semin Cancer Biol, 16:420–426. 2006.
13.
AzamS, JouvetN, JilaniA, VongsamphanhR, YangX, YangS, RamotarD. Human glyceraldehyde-3-phosphate dehydrogenase plays a direct role in reactivating oxidized forms of the DNA repair enzyme APE1. J Biol Chem, 283:30632–30641. 2008.
14.
BapatA, FishelML, KelleyMR. Going ape as an approach to cancer therapeutics. Antioxid Redox Signal, 11:651–669. 2009.
15.
BarnesT, KimWC, ManthaAK, KimSE, IzumiT, MitraS, LeeCH. Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA. Nucleic Acids Res, 37:3946–3958. 2009.
16.
BeckmanRA, LoebLA. Efficiency of carcinogenesis with and without a mutator mutation. Proc Natl Acad Sci U S A, 103:14140–14145. 2006.
17.
BeerninkPT, SegelkeBW, HadiMZ, ErzbergerJP, WilsonDMI, RuppB. Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implication for the catalytic mechanism. J Mol Biol, 307:1023–1034. 2001.
18.
BennettSE, KitnerJ. Characterization of the aldehyde reactive probe reaction with AP-sites in DNA: influence of AP-lyase on adduct stability. Nucleosides Nucleotides Nucleic Acids, 25:823–842. 2006.
19.
BhakatKK, ManthaAK, MitraS. Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal, 11:621–638. 2009.
20.
BiaglowJE, MillerRA. The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther, 4:6–13. 2005.
21.
BindraRS, SchafferPJ, MengA, WooJ, MaseideK, RothME, LizardiP, HedleyDW, BristowRG, GlazerPM. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol, 24:8504–8518. 2004.
22.
BindraRS, SchafferPJ, MengA, WooJ, MaseideK, RothME, LizardiP, HedleyDW, BristowRG, GlazerPM. Alterations in DNA repair gene expression under hypoxia: elucidating the mechanisms of hypoxia-induced genetic instability. Ann N Y Acad Sci, 1059:184–195. 2005.
23.
BindraRS, CrosbyME, GlazerPM. Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev, 26:249–260. 2007.
24.
BindraRS, GlazerPM. Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia. Oncogene, 26:2048–2057. 2007.
25.
BindraRS, GlazerPM. Co-repression of mismatch repair gene expression by hypoxia in cancer cells: role of the Myc/Max network. Cancer Lett, 252:93–103. 2007.
26.
BishopAJ, HollanderMC, KosarasB, SidmanRL, FornaceAJJr, SchiestlRH. Atm-, p53-, and Gadd45a-deficient mice show an increased frequency of homologous recombination at different stages during development. Cancer Res, 63:5335–5343. 2003.
27.
BlessingH, KrausS, HeindlP, BalW, HartwigA. Interaction of selenium compounds with zinc finger proteins involved in DNA repair. Eur J Biochem, 271:3190–3299. 2004.
28.
BobolaMS, FinnLS, EllenbogenRG, GeyerJR, BergerMS, BragaJM, MeadeEH, GrossME, SilberJR. Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors. Clin Cancer Res, 11:7405–7414. 2005.
29.
BozonetSM, FindlayVJ, DayAM, CameronJ, VealEA, MorganBA. Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide. J Biol Chem, 280:23319–23327. 2005.
30.
BravardA, VacherM, GougetB, CoutantA, de BoisferonFH, MarsinS, ChevillardS, RadicellaJP. Redox regulation of human OGG1 activity in response to cellular oxidative stress. Mol Cell Biol, 26:7430–7436. 2006.
31.
BravardA, VacherM, MoritzE, VaslinL, HallJ, EpeB, RadicellaJP. Oxidation status of human OGG1-S326C polymorphic variant determines cellular DNA repair capacity. Cancer Res, 69:3642–3649. 2009.
32.
BristowRG, HillRP. Hypoxia and metabolism: hypoxia, DNA repair and genetic instability. Nat Rev Cancer, 8:180–192. 2008.
33.
Burke-GaffneyA, CallisterME, NakamuraH. Thioredoxin: friend or foe in human disease?Trends Pharmacol Sci, 26:398–404. 2005.
34.
BurmaS, ChenBP, ChenDJ. Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. DNA Repair (Amst), 5:1042–1048. 2006.
35.
CaoX, KambeF, OhmoriS, SeoH. Oxidoreductive modification of two cysteine residues in paired domain by Ref-1 regulates DNA-binding activity of Pax-8. Biochem Biophys Res Commun, 297:288–293. 2002.
36.
ChenDS, HermanT, DempleB. Two distinct human DNA diesterases that hydrolyze 3'-blocking deoxyribose fragments from oxidized DNA. Nucleic Acids Res, 19:5907–5914. 1991.
37.
ChenDS, OlkowskiZL. Biological responses of human apurinic endonuclease to radiation-induced DNA damage. Ann N Y Acad Sci, 726:306–308. 1994.
38.
ChenJ, SadowskiI. Identification of the mismatch repair genes PMS2 and MLH1 as p53 target genes by using serial analysis of binding elements. Proc Natl Acad Sci U S A, 102:4813–4818. 2005.
39.
ChewEH, LuJ, BradshawTD, HolmgrenA. Thioredoxin reductase inhibition by antitumor quinols: a quinol pharmacophore effect correlating to antiproliferative activity. FASEB J, 22:2072–2083. 2008.
40.
ChristmannM, TomicicMT, RoosWP, KainaB. Mechanisms of human DNA repair: an update. Toxicology, 193:3–34. 2003.
41.
ClapperML. Chemopreventive activity of oltipraz. Pharmacol Ther, 78:17–27. 1998.
42.
DamiaG, D'IncalciM. Targeting DNA repair as a promising approach in cancer therapy. Eur J Cancer, 43:1791–1801. 2007.
43.
DavidSS, WilliamsSD. Chemistry of glycosylases and endonucleases involved in base-excision repair. Chem Rev, 98:1221–1262. 1998.
44.
De BontR, van LarebekeN. Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis, 19:169–185. 2004.
45.
DempleB, HarrisonL. Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem, 63:915–948. 1994.
46.
DoetschPW, CunninghamRP. The enzymology of apurinic/apyrimidinic endonucleases. Mutat Res, 236:173–201. 1990.
47.
EkerAP, QuayleC, ChavesI, van der HorstGT. DNA repair in mammalian cells: direct DNA damage reversal: elegant solutions for nasty problems. Cell Mol Life Sci, 66:968–980. 2009.
48.
EmaM, HirotaK, MimuraJ, AbeH, YodoiJ, SogawaK, PoellingerL, Fujii-KuriyamaY. Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J, 18:1905–1914. 1999.
49.
EssersJ, van SteegH, de WitJ, SwagemakersSM, VermeijM, HoeijmakersJH, KanaarR. Homologous and non-homologous recombination differentially affect DNA damage repair in mice. EMBO J, 19:1703–1710. 2000.
50.
EvansAR, Limp-FosterM, KelleyMR. Going APE over Ref-1. Mutat Res, 461:83–108. 2000.
51.
FanJ, WilsonDM3rd. Protein-protein interactions and posttranslational modifications in mammalian base excision repair. Free Radic Biol Med, 38:1121–1138. 2005.
FarmerH, McCabeN, LordCJ, TuttAN, JohnsonDA, RichardsonTB, SantarosaM, DillonKJ, HicksonI, KnightsC, MartinNM, JacksonSP, SmithGC, AshwortA. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 434:917–921. 2005.
54.
FernandesAP, HolmgrenA. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antioxid Redox Signal, 6:63–74. 2004.
55.
FischerJL, LanciaJK, MathurA, SmithML. Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex. Anticancer Res, 26:899–904. 2006.
56.
FishelML, HeY, SmithML, KelleyMR. Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide. Clin Cancer Res, 13:260–267. 2007.
57.
FishelML, KelleyMR. The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. Mol Aspects Med, 28:375–395. 2007.
58.
FishelML, HeY, ReedAM, Chin-SinexH, HutchinsGD, MendoncaMS, KelleyMR. Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst), 7:177–186. 2008.
FleckO, NielsenO. DNA repair. J Cell Sci, 117:515–517. 2004.
61.
Forman-KayJD, CloreGM, GronenbornAM. Relationship between electrostatics and redox function in human thioredoxin: characterization of pH titration shifts using two-dimensional homo- and heteronuclear NMR. Biochemistry, 31:3442–3452. 1992.
FriedbergEC. How nucleotide excision repair protects against cancer. Nat Rev Cancer, 1:22–33. 2001.
64.
FrosinaG, FortiniP, RossiO, CarrozzinoF, AbbondandoloA, DogliottiE. Repair of abasic sites by mammalian cell extracts. Biochem J, 304:699–705. 1994.
65.
FungH, DempleB. A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells. Mol Cell, 17:463–470. 2005.
66.
FungH, LiuP, DempleB. ATF4-dependent oxidative induction of the DNA repair enzyme Ape1 counteracts arsenite cytotoxicity and suppresses arsenite-mediated mutagenesis. Mol Cell Biol, 27:8834–8847. 2007.
67.
GaiddonC, MoorthyNC, PrivesC. Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. EMBO J, 18:5609–5621. 1999.
68.
GeorgiadisM, LuoM, GaurR, DelaplaneS, LiX, KelleyM. Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease. Mutat Res, 643:54–63. 2008.
69.
GilesNM, GilesGI, JacobC. Multiple roles of cysteine in biocatalysis. Biochem Biophys Res Commun, 300:1–4. 2003.
70.
GormanMA, MoreraS, RothwellDG, La FortelleE, MolCD, TainerJA, HicksonID, FreemontPS. The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites. EMBO J, 16:6548–6558. 1997.
71.
GrayMJ, ZhangJ, EllisLM, SemenzaGL, EvansDB, WatowichSS, GallickGE. HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene, 24:3110–3120. 2005.
72.
GrombacherT, EichhornU, KainaB. p53 is involved in regulation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) by DNA damaging agents. Oncogene, 17:845–851. 1998.
73.
GroschS, KainaB. Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB. Biochem Biophys Res Commun, 261:859–863. 1999.
74.
GuoY, ChenJ, ZhaoT, FanZ. Granzyme K degrades the redox/DNA repair enzyme Ape1 to trigger oxidative stress of target cells leading to cytotoxicity. Mol Immunol, 45:2225–2235. 2008.
75.
HainautP, MilnerJ. Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res, 53:469–44. 1993.
76.
HandelML, WattsCK, deFazioA, DayRO, HerlandRL. Inhibition of AP-1 binding and transcription by gold and selenium involving conserved cysteine residues in Jun and Fos. Proc Natl Acad Sci U S A, 92,10:4497–4491. 1995.
77.
HansonS, KimE, DeppertW. Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization. Oncogene, 24:1641–1647. 2005.
78.
HayakawaJ, MittalS, WangY, KorkmazKS, AdamsonE, EnglishC, OhmichiM, McClellandM, MercolaD. Identification of promoters bound by c-Jun/ATF2 during rapid large-scale gene activation following genotoxic stress. Mol Cell, 16:521–535. 2004.
79.
HeF, YangXP, SrivastavaDK, WilsonSH. DNA polymerase beta gene expression: the promoter activator CREB-1 is upregulated in Chinese hamster ovary cells by DNA alkylating agent-induced stress. Biol Chem, 384:19–23. 2003.
80.
HeltonES, ChenX. p53 modulation of the DNA damage response. J Cell Biochem, 100:883–8896. 2007.
81.
HerringCJ, WestCM, WilksDP, DavidsonSE, HunterRD, BerryP, ForsterG, MacKinnonJ, RaffertyJA, ElderRH, HendryJH, MargisonGP. Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers. Br J Cancer, 78:1128–1133. 1998.
82.
HessJ, AngelP, Schorpp-KistnerM. AP-1 subunits: quarrel and harmony among siblings. J Cell Sci, 117:5965–5973. 2004.
83.
HirotaK, MatsuiM, IwataS, NishiyamaA, MoriK, YodoiJ. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A, 94:3633–3638. 1997.
84.
HirotaK, MurataM, SachiY, NakamuraH, TakeuchiJ, MoriK, YodoiJ. Distinct roles of thioredoxin in the cytoplasm and in the nucleus: a two-step mechanism of redox regulation of transcription factor NF-kappaB. J Biol Chem, 274:27891–27897. 1999.
85.
HoeijmakersJH. DNA repair mechanisms. Maturitas, 38:17–22discussion 22–232001.
86.
HoeijmakersJH. Genome maintenance mechanisms for preventing cancer. Nature, 411:366–374. 2001.
HolWG. The role of the alpha-helix dipole in protein function and structure. Prog Biophys Mol Biol, 45:149–195. 1985.
89.
HollanderMC, PhilburnRT, PattersonAD, Velasco-MiguelS, FriedbergEC, LinnoilaRI, FornaceAJJr. Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis. Proc Natl Acad Sci U S A, 102:13200–12305. 2005.
90.
HolmgrenA. Thioredoxin and glutaredoxin systems. J Biol Chem, 264:13963–13966. 1989.
91.
HolmgrenA. Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide. Structure, 3:239–243. 1995.
92.
HromasR, WrayJ, LeeSH, MartinezL, FarringtonJ, CorwinLK, RamseyH, NickoloffJA, WilliamsonEA. The human set and transposase domain protein Metnase interacts with DNA Ligase IV and enhances the efficiency and accuracy of non-homologous end-joining. DNA Repair (Amst), 7:1927–1937. 2008.
93.
HuangLE, AranyZ, LivingstonDM, BunnHF. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem, 271:32253–32259. 1996.
94.
HuangRP, AdamsonED. Characterization of the DNA-binding properties of the early growth response-1 (Egr-1) transcription factor: evidence for modulation by a redox mechanism. DNA Cell Biol, 12:265–273. 1993.
95.
HumbertO, AchourI, LautierD, LaurentG, SallesB. hMSH2 expression is driven by AP1-dependent regulation through phorbol-ester exposure. Nucleic Acids Res, 31:5627–5634. 2003.
96.
HwangBJ, FordJM, HanawaltPC, ChuG. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci U S A, 96:424–428. 1999.
97.
IliopoulosO, LevyAP, JiangC, KaelinWGJr, GoldbergMA. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci U S A, 93:10595–10599. 1996.
98.
IvanM, KondoK, YangH, KimW, ValiandoJ, OhhM, SalicA, AsaraJM, LaneWS, KaelinWGJr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science, 292:464–468. 2001.
99.
IzumiT, BrownDB, NaiduCV, BhakatKK, MacinnesMA, SaitoH, ChenDJ, MitraS. Two essential but distinct functions of the mammalian abasic endonuclease. Proc Natl Acad Sci U S A, 102:5739–5743. 2005.
100.
JacobC, GilesGI, GilesNM, SiesH. Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed Engl, 42:4742–4758. 2003.
101.
JayaramanL, MurthyKG, ZhuC, CurranT, XanthoudakisS, PrivesC. Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes Dev, 11:558–570. 1997.
102.
JiangBH, RueE, WangGL, RoeR, SemenzaGL. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem, 271:17771–17778. 1996.
103.
JiangY, GuoC, VaskoMR, KelleyMR. Implications of apurinic/apyrimidinic endonuclease in reactive oxygen signaling response after cisplatin treatment of dorsal root ganglion neurons. Cancer Res, 68:6425–6434. 2008.
KainaB, ChristmannM, NaumannS, RoosWP. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst), 6:1079–1099. 2007.
106.
KelleyMR, FishelML. DNA repair proteins as molecular targets for cancer therapeutics. Anticancer Agents Med Chem, 8:417–425. 2008.
107.
KhanN, AfaqF, MukhtarH. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal, 10:475–510. 2008.
108.
KondoN, NakamuraH, MasutaniH, YodoiJ. Redox regulation of human thioredoxin network. Antioxid Redox Signal, 8:1881–1890. 2006.
KrumanII, WerstoRP, Cardozo-PelaezF, SmilenovL, ChanSL, ChrestFJ, EmokpaeRJr, GorospeM, MattsonMP. Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron, 41:549–561. 2004.
111.
KunzC, SaitoY, ScharP. DNA Repair in mammalian cells: mismatched repair: variations on a theme. Cell Mol Life Sci, 66:1021–1038. 2009.
112.
LandoD, PongratzI, PoellingerL, WhitelawML. A redox mechanism controls differential DNA binding activities of hypoxia-inducible factor (HIF) 1alpha and the HIF-like factor. J Biol Chem, 275:4618–4627. 2000.
113.
LaneDP. Cancer: p53, guardian of the genome. Nature, 358:15–16. 1992.
114.
LangieSA, KnaapenAM, HoubenJM, van KempenFC, de HoonJP, GottschalkRW, GodschalkRW, van SchootenFJ. The role of glutathione in the regulation of nucleotide excision repair during oxidative stress. Toxicol Lett, 168:302–309. 2007.
115.
LauJP, WeatherdonKL, SkalskiV, HedleyDW. Effects of gemcitabine on APE/ref-1 endonuclease activity in pancreatic cancer cells, and the therapeutic potential of antisense oligonucleotides. Br J Cancer, 91:1166–1173. 2004.
116.
LavonI, FuchsD, ZrihanD, EfroniG, ZelikovitchB, FelligY, SiegalT. Novel mechanism whereby nuclear factor kappaB mediates DNA damage repair through regulation of O(6)-methylguanine-DNA-methyltransferase. Cancer Res, 67:8952–8959. 2007.
117.
LeeSH, OshigeM, DurantST, RasilaKK, WilliamsonEA, RamseyH, KwanL, NickoloffJA, HromasR. The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair. Proc Natl Acad Sci U S A, 102:18075–18080. 2005.
118.
LehmannAR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie, 85:1101–1111. 2003.
119.
LiQ, ZhangL, TsangB, GardnerK, Bostick-BrutonF, ReedE. Phorbol ester exposure activates an AP-1-mediated increase in ERCC-1 messenger RNA expression in human ovarian tumor cells. Cell Mol Life Sci, 55:456–466. 1999.
120.
LilligCH, HolmgrenA. Thioredoxin and related molecules: from biology to health and disease. Antioxid Redox Signal, 9:25–47. 2007.
LiuF, FuY, MeyskensFLJr. MiTF regulates cellular response to reactive oxygen species through transcriptional regulation of APE-1/ref-1. J Invest Dermatol, 129:422–431. 2009.
123.
LiuZ, HuangSL, LiMM, HuangZS, LeeKS, GuLQ. Inhibition of thioredoxin reductase by mansonone F analogues: implications for anticancer activity. Chem Biol Interact, 177:48–57. 2009.
124.
LiuzziM, Talpaert-BorleM. A new approach to the study of the base-excision repair pathway using methoxyamine. J Biol Chem, 260:5252–5258. 1985.
125.
LobodaA, StachurskaA, DoroszJ, ZurawskiM, WegrzynJ, KozakowskaM, JozkowiczA, DulakJ. HIF-1 attenuates Ref-1 expression in endothelial cells: reversal by siRNA and inhibition of geranylgeranylation. Vasc Pharmacol, 51:133–139. 2009.
126.
Lopez de SaroFJ, MarinusMG, ModrichP, O'DonnellM. The beta sliding clamp binds to multiple sites within MutL and MutS. J Biol Chem, 281:14340–14349. 2006.
127.
LuX, LozanoG, DonehowerLA. Activities of wildtype and mutant p53 in suppression of homologous recombination as measured by a retroviral vector system. Mutat Res, 522:69–83. 2003.
128.
LuoM, DelaplaneS, JiangA, ReedA, HeY, FishelM, Nyland IIRL, BorchRF, QiaoX, GeorgiadisMM, KelleyMR. Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small molecule inhibition of Ape1's redox function. Antioxid Redox Signal, 10:1853–1867. 2008.
129.
MadhusudanS, HicksonID. DNA repair inhibition: a selective tumour targeting strategy. Trends Mol Med, 11:503–511. 2005.
130.
MadhusudanS, SmartF, ShrimptonP, ParsonsJL, GardinerL, HoulbrookS, TalbotDC, HammondsT, FreemontPA, SternbergMJ, DianovEL, HicksonID. Isolation of a small molecule inhibitor of DNA base excision repair. Nucleic Acids Res, 33:4711–4724. 2005.
131.
MathersJC, CoxheadJM, TysonJ. Nutrition and DNA repair: potential molecular mechanisms of action. Curr Cancer Drug Targets, 7:425–431. 2007.
132.
MaxwellPH, WiesenerMS, ChangGW, CliffordSC, VauxEC, CockmanME, WykoffCC, PughCW, MaherER, RatcliffePJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 399:271–275. 1999.
133.
McEligotAJ, YangS, MeyskensFLJr. Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells. Annu Rev Nutr, 25:261–295. 2005.
134.
McNeillDR, WilsonDM3rd. A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents. Mol Cancer Res, 5:61–70. 2007.
135.
MengAX, JalaliF, CuddihyA, ChanN, BindraRS, GlazerPM, BristowRG. Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncol, 76:168–176. 2005.
136.
MerluzziS, GriG, GatteiV, PaganoM, PucilloC. APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation. Mol Immunol, 45:3731–3739. 2008.
137.
MessinaM, KucukO, LampeJW. An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J AOAC Int, 89:1121–1134. 2006.
138.
MihaylovaVT, BindraRS, YuanJ, CampisiD, NarayananL, JensenR, GiordanoF, JohnsonRS, RockwellS, GlazerPM. Decreased expression of the DNA mismatch repair gene Mlh1 under hypoxic stress in mammalian cells. Mol Cell Biol, 23:3265–3273. 2003.
139.
MolCD, IzumiT, MitraS, TainerJA. DNA-bound structure and mutants reveal abasic DNA binding by APE1 DNA repair and coordination. Nature, 403:451–455. 2000.
140.
MooreDH, MichaelH, TrittR, ParsonsSH, KelleyMR. Alterations in the expression of the DNA repair/redox enzyme APE/ref-1 in epithelial ovarian cancers. Clin Cancer Res, 6:602–609. 2000.
141.
MukherjeeA, MartinSG. The thioredoxin system: a key target in tumour and endothelial cells. Br J Radiol, 81:S57–S68. 2008.
142.
NakamuraH, NakamuraK, YodoiJ. Redox regulation of cellular activation. Annu Rev Immunol, 15:351–369. 1997.
143.
NakamuraH. Thioredoxin and its related molecules: update 2005. Antioxid Redox Signal, 7:823–828. 2005.
144.
NouspikelT. DNA repair in mammalian cells: nucleotide excision repair: variations on versatility. Cell Mol Life Sci, 66:994–1009. 2009.
145.
NouspikelT. DNA repair in mammalian cells: So DNA repair really is that important?Cell Mol Life Sci, 66:965–967. 2009.
146.
O'DwyerPJ, JohnsonSW, KhaterC, KruegerA, MatsumotoY, HamiltonTC, YaoKS. The chemopreventive agent oltipraz stimulates repair of damaged DNA. Cancer Res, 57:1050–1053. 1997.
147.
OnoY, FurutaT, OhmotoT, AkiyamaK, SekiS. Stable expression in rat glioma cells of sense and antisense nucleic acids to a human multifunctional DNA repair enzyme, APEX nuclease. Mutat Res, 315:55–63. 1994.
148.
OrdwayJM, EberhartD, CurranT. Cysteine 64 of Ref-1 is not essential for redox regulation of AP-1 DNA binding. Mol Cell Biol, 23:4257–4266. 2003.
149.
OzakiM, SuzukiS, IraniK. Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase. FASEB J, 16:889–890. 2002.
150.
PardoB, Gomez-GonzalezB, AguileraA. DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship. Cell Mol Life Sci, 66:1039–1056. 2009.
151.
ParkWS, KoEA, JungID, SonYK, KimHK, KimN, ParkSY, HongKW, ParkYM, ChoiTH, HanJ. APE1/Ref-1 promotes the effect of angiotensin II on Ca2+ -activated K+ channel in human endothelial cells via suppression of NADPH oxidase. Arch Pharm Res, 31:1291–1301. 2008.
152.
PinesA, PerroneL, BiviN, RomanelloM, DamanteG, GulisanoM, KelleyMR, QuadrifoglioF, TellG. Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP. Nucleic Acids Res, 33:4379–4394. 2005.
153.
PowisG, MontfortWR. Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol, 41:261–195. 2001.
154.
RaffelJ, BhattacharyyaAK, GallegosA, CuiH, EinspahrJG, AlbertsDS, PowisG. Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival. J Lab Clin Med, 142:46–51. 2003.
155.
RaffertyJA, ClarkeAR, SellappanD, KorefMS, FraylingIM, MargisonGP. Induction of murine O6-alkylguanine-DNA-alkyltransferase in response to ionising radiation is p53 gene dose dependent. Oncogene, 12:693–697. 1996.
156.
RaffoulJJ, BanerjeeS, Singh-GuptaV, KnollZE, FiteA, ZhangH, AbramsJ, SarkarFH, HillmanGG. Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo. Cancer Res, 67:2141–2149. 2007.
157.
RobertsonAB, KlunglandA, RognesT, LeirosI. DNA repair in mammalian cells: base excision repair: the long and short of it. Cell Mol Life Sci, 66:981–993. 2009.
158.
RuggeriBA, RobinsonC, AngelesT, WilkinsonJT, ClapperML. The chemopreventive agent oltipraz possesses potent antiangiogenic activity in vitro, ex vivo, and in vivo and inhibits tumor xenograft growth. Clin Cancer Res, 8:267–274. 2002.
159.
SchererSJ, MaierSM, SeifertM, HanselmannRG, ZangKD, Muller-HermelinkHK, AngelP, WelterC, SchartlM. p53 and c-Jun functionally synergize in the regulation of the DNA repair gene hMSH2 in response to UV. J Biol Chem, 275:37469–37473. 2000.
160.
SchwartzEI, SmilenovLB, PriceMA, OsredkarT, BakerRA, GhoshS, ShiFD, VollmerTL, LencinasA, StearnsDM, GoropseM, KrumanII. Cell cycle activation in postmitotic neurons is essential for DNA repair. Cell Cycle, 6:318–329. 2007.
161.
SeipleLA, CardellinaJH2nd, AkeeR, StiversJT. Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids. Mol Pharmacol, 73:669–677. 2008.
162.
SenguptaS, HarrisCC. p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol, 6:44–55. 2005.
SungP, KleinH. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol, 7:739–750. 2006.
168.
TanT, ChuG. p53 Binds and activates the xeroderma pigmentosum DDB2 gene in humans but not mice. Mol Cell Biol, 22:3247–3254. 2002.
169.
TellG, ZeccaA, PellizzariL, SpessottoP, ColombattiA, KelleyMR, DamanteG, PucilloC. An “environment to nucleus” signaling system operates in B lymphocytes: redox status modulates BSAP/Pax-5 activation through Ref-1 nuclear translocation. Nucleic Acids Res, 28:1099–1105. 2002.
170.
TellG, DamanteG, CaldwellD, KelleyMR. The intracellular localization of APE1/Ref-1: more than a passive phenomenon?Antioxid Redox Signal, 7:367–384. 2005.
171.
TellG, QuadrifoglioF, TiribelliC, KelleyMR. The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal, 11:601–620. 2009.
172.
ToKK, KoshijiM, HammerS, HuangLE. Genetic instability: the dark side of the hypoxic response. Cell Cycle, 4:881–882. 2005.
173.
ToKK, SedelnikovaOA, SamonsM, BonnerWM, HuangLE. The phosphorylation status of PAS-B distinguishes HIF-1alpha from HIF-2alpha in NBS1 repression. EMBO J, 25:4784–4794. 2006.
174.
TornalettiS. DNA repair in mammalian cells: transcription-coupled DNA repair: directing your effort where it's most needed. Cell Mol Life Sci, 66:1010–1020. 2009.
VascottoC, FantiniD, RomanelloM, CesarattoL, DeganutoM, LeonardiA, RadicellaJP, KelleyMR, D'AmbrosioC, ScaloniA, QuadrifoglioF, TellG. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol, 29:1834–1854. 2009.
177.
VivancosAP, CastilloEA, BiteauB, NicotC, AyteJ, ToledanoMB, HidalgoE. A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proc Natl Acad Sci U S A, 102:8875–8880. 2005.
178.
WalkerLJ, RobsonCN, BlackE, GillespieD, HicksonID. Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding. Mol Cell Biol, 13:5370–5376. 1993.
179.
WalkerLJ, CraigRB, HarrisAL, HicksonID. A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. Nucleic Acids Res, 22:4884–4889. 1994.
180.
WangD, LuoM, KelleyMR. 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, 3:679–686. 2004.
181.
WeichselA, GasdaskaJR, PowisG, MontfortWR. Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer. Structure, 4:735–751. 2996.
182.
WoodRD, MitchellM, LindahlT. Human DNA repair genes. Mutat Res, 577:275–283. 2005
183.
WoodZA, PooleLB, KarplusPA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science, 300:650–653. 2003.
184.
XanthoudakisS, CurranT. Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. EMBO J, 11:653–665. 1992.
185.
XanthoudakisS, MiaoG, WangF, PanYC, CurranT. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J, 11:3323–3335. 1992.
186.
XanthoudakisS, MiaoGG, CurranT. The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. Proc Natl Acad Sci U S A, 91:23–27. 1994.
187.
XanthoudakisS, CurranT. Redox regulation of AP-1: a link between transcription factor signaling and DNA repair. Adv Exp Med Biol, 387:69–75. 1996.
188.
XanthoudakisS, SmeyneRJ, WallaceJD, CurranT. The redox/DNA repair protein, Ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci U S A, 93:8919–8923. 1996.
189.
XuJ, MorrisGF. p53-mediated regulation of proliferating cell nuclear antigen expression in cells exposed to ionizing radiation. Mol Cell Biol, 19:12–20. 1999.
190.
XuY, MooreDH, BroshearsJ, LiuL, WilsonTM, KelleyMR. The apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme is elevated in premalignant and malignant cervical cancer. Anticancer Res, 17:3713–3719. 1997.
191.
YamabeY, ShimamotoA, GotoM, YokotaJ, SugawaraM, FuruichiY. Sp1-mediated transcription of the Werner helicase gene is modulated by Rb and p53. Mol Cell Biol, 18:6191–6200. 1998.
192.
YamawakiH, BerkBC. Thioredoxin: a multifunctional antioxidant enzyme in kidney, heart and vessels. Curr Opin Nephrol Hypertens, 14:149–153. 2005.
193.
YangS, IraniK, HeffronSE, JurnakF, MeyskensFLJr. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/Ref-1) in human melanoma and identification of the therapeutic potential of resveratrol as an APE/Ref-1 inhibitor. Mol Cancer Ther, 4:1923–1935. 2005.
194.
YaoKS, HageboutrosA, FordP, O'DwyerPJ. Involvement of activator protein-1 and nuclear factor-kappaB transcription factors in the control of the DT-diaphorase expression induced by mitomycin C treatment. Mol Pharmacol, 51:422–430. 1997.
195.
YounBW, FialaES, SohnOS. Mechanisms of organoselenium compounds in chemoprevention: effects on transcription factor-DNA binding. Nutr Cancer, 40:28–33. 2001.
196.
ZakyA, BussoC, IzumiT, ChattopadhyayR, BassiounyA, MitraS, BhakatKK. Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage. Nucleic Acids Res, 36:1555–1566. 2008.
197.
ZawahirZ, DayamR, DengJ, PereiraC, NeamatiN. Pharmacophore guided discovery of small-molecule human apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem, 52:20–32. 2009.
198.
ZielKA, CampbellCC, WilsonGL, GillespieMN. Ref-1/Ape is critical for formation of the hypoxia-inducible transcriptional complex on the hypoxic response element of the rat pulmonary artery endothelial cell VEGF. FASEB J Epub, 2004.
199.
ZouGM, LuoMH, ReedA, KelleyMR, YoderMC. Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain. Blood, 109:1917–1922. 2007.
200.
ZouGM, MaitraA. Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration. Mol Cancer Ther, 7:2012–2021. 2008.
201.
ZouGM, KarikariC, KabeY, HandaH, AndersRA, MaitraA. The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: therapeutic implications in tumor angiogenesis. J Cell Physiol, 219:209–218. 2009.
202.
ZurerI, HofsethLJ, CohenY, Xu-WelliverM, HussainSP, HarrisCC, RotterV. The role of p53 in base excision repair following genotoxic stress. Carcinogenesis, 25:11–19. 2004.
