Abstract
This chapter entitled “Cell Cycle, DNA Damage Repair Systems, and Impact of Redox Regulation in Cancer” introduces the cell cycle components in normal cells and further discusses regulators involvement in cell cycle checkpoints, cyclin-CDK interaction, and activation. Cell cycle inhibitors, transcription regulatory network, redox oscillation, and metabolic activity in cell cycle were discussed. All these events are further examined in the context of cancer cells, highlighting the differences from normal cell situations.
Further, the DNA damage repair system with repair pathways involving various enzymatic systems has been described. Oxidative stress inducing genomic instability and cancer development has been introduced. Apurinic/apyrimidinic 1 (APE1) and oxidative DNA damage repair have been discussed, focusing on their dual action as repair and redox reactions. The impact of redox reaction in DNA repair, DNA damage response (DDR), and cancer therapy strategies has been discussed at length. PARP inhibitors of DDR, other inhibitors such as ATM, ATR, and DNA-PKCs (regulation of DDR signaling), and further involvement of synthetic lethality concept for cancer therapy have been discussed.
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References
Abbotts R, Wilson DM (2017) III coordination of DNA single strand break repair. Free Radic Biol Med 107:228–244
Almeida A, Bolanos JP, Moncada S (2010) E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferation. Proc Natl Acad Sci U S A 107:738–741
Altieri F, Grillo C, Maceroni M, Chichiarelli S (2008) DNA damage and repair: from molecular mechanisms to health implications. Antioxid Redox Signal 10:891–937
Ando K, Hirao S, Kabe Y, Ogura Y, Sato I et al (2008) A new APE1/Ref-1-dependent pathway leading to reduction of NF-kappaB and AP-1, and activation of their DNA-binding activity. Nucleic Acids Res 36:4327–4336
Andor N, Maley CC, Ji HP (2017) Genomic instability in cancer: teetering on the limit of tolerance. Cancer Res 77:2179–2185
Angkeow P, Deshpande SS, Qi B, Liu YX, Park YC, Jeon BH et al (2002) Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative stress and apoptosis. Cell Death Differ 9:717–725
Atilla-Gokcumen GE, Muro E, Relat-Goberna J, Sasse S, Bedigian A, Coughlin ML, Garcia-Manyes S, Eggert US (2014) Dividing cells regulate their lipid composition and localization. Cell 156:428–439
Attwooll C, Lazzerini Denchi E, Helin K (2004) The E2F family: specific functions and overlapping interests. EMBO J 23:4709–4716
Azam S, Jouvet N, Jilani A, Vongsamphanh R, Yang X, Yang S, Ramotar D (2008) 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
Bagella L, Sun A, Tonini T, Abbadessa G, Cottone G, Paggi MG, DeLuca A, Claudio PP, Giordano A (2007) A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo. Oncogene 26:1829–1939
Bajad SU, Lu W, Kimball EH, Yuan J, Peterson C, Rabinowitz JD (2006) Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry. J Chromatogr A 1125:76–88
Bapat A, Fishel ML, Kelley MR (2009) Going ape as an approach to cancer therapeutics. Antioxid Redox Signal 11:651–667
Bapat A, Glass LS, Luo M, Fishel ML, Long EC, Georgiadis MM et al (2010) Novel small-molecule inhibitor of apurinic/apyrimidinic endonuclease 1 blocks proliferation and reduces viability of glioblastoma cells. J Pharmacol Exp Ther 334:988–998
Barford D (2011) Structure, function and mechanism of the anaphase promoting complex (APC/C). Q Rev Biophys 44:153–190
Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214
Barnum KJ, O’Connell MJ (2014) Cell cycle regulation by checkpoints. Methods Mol Biol 1170:29–40
Barriere C, Santamaria D, Cerqueira A, Galan J, Martin A, Ortega S et al (2007) Mice thrive without Cdk4 and Cdk2. Mol Oncol 1:72–83
Barzilay G, Hickson ID (1995) Structure and function of apurinic/apyrimidinic endonucleases. BioEssays 17:713–719
Bennett RAO, Wilson DM, Wong D, Demple B (1997) Interaction of human apurinic endonuclease and DNA polymerase β in the base excision repair pathway. Proc Natl Acad Sci U S A 94:7166–7169
Bhakat KK, Mantha AK, Mitra S (2009) Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal 11:621–637
Blain SW (2008) Switching cyclin D-Cdk4 kinase activity on and off. Cell Cycle 7:892–898
Blanchet E, Annicotte JS, Lagarrigue S, Aguilar V, Clapé C, Chavey C, Fritz V, Casas F, Apparailly F, Auwerx J et al (2011) E2F transcription factor-1 regulates oxidative metabolism. Nat Cell Biol 13:1146–1152
Boonstra J, Post JA (2004) Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 337:1–13
Boren J, Montoya AR, de Atauri P, Comin-Anduix B, Cortes A, Centelles JJ et al (2002) Metabolic control analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development. Mol Biol Rep 29:7–12
Bouwman P, Jonkers J (2012) The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer 12:587–598
Branzei D, Foiani M (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9:297–308
Brenerman BM, Illuzzi JL, Wilson DM 3rd (2014) Base excision repair capacity in informing healthspan. Carcinogenesis 35:2643–2652
Brown JS, O’Carrigan B, Jackson SP, Yap TA (2016) Targeting DNA repair in cancer: beyond PARP inhibitors. Cancer Discov 7:1–18
Brown JS, O’Carrigan B, Jackson SP, Yap TA (2017) Targeting DNA repair in cancer: beyond PARP inhibitors. Cancer Discov 7:20–37
Buettner GR, Ng CF, Wang M, Rodgers VG, Schafer FQ (2006) A new paradigm: manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. Free Radic Biol Med 41:1338–1350
Bukhari AB, Lewis CW, Pearce JJ, Luong D, Chan GK, Gamper AM (2019) Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis. J Clin Invest 129:1329–1344
Burch PM, Heintz NH (2005) Redox regulation of cell-cycle re-entry: cyclin D1 as a primary target for the mitogenic effects of reactive oxygen and nitrogen species. Antioxid Redox Signal 7:741–751
Burch PM, Yuan Z, Loonen A, Heintz NH (2004) An extracellular signal-regulated kinase 1- and 2-dependent program of chromatin trafficking of c-Fos and Fra-1 is required for cyclin D1 expression during cell cycle re-entry. Mol Cell Biol 24:4696–4709
Burger K, Gullerova M (2015) Swiss army knives: non-canonical functions of nuclear Drosha and Dicer. Nat Rev Mol Cell Biol 16:417–430
Burger K, Schlackow M, Potts M, Hester S, Mohammed S, Gullerova M (2017) Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage. J Cell Biol 216:2373–2389
Burhans WC, Heintz NH (2009) The cell cycle is a redox cycle: linking phase-specific targets to cell fate. Free Radic Biol Med 47:1282–1293
Cadet J, Douki T, Ravanat JL (2015) Oxidatively generated damage to cellular DNA by UVB and UVA radiation. Photochem Photobiol 91:140–155
Caldecott KW (2014) DNA single-strand break repair. Exp Cell Res 329:2–8
Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD (2004) A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell 16:399–411
Canaverse M, Santo L, Raje N (2012) Cyclin dependent kinase in cancer. Cancer Biol Ther 13:451–457
Canbay E, Agachan B, Gulluoglu M, Isbir T, Balik E, Yamaner S et al (2010) Possible associations of APE1 polymorphism with susceptibility and HOGG1 polymorphism with prognosis in gastric cancer. Anticancer Res 30:1359–1364
Cao Q, Qin C, Meng X, Ju X, Ding Q, Wang M et al (2011) Genetic polymorphisms in APE1 are associated with renal cell carcinoma risk in a Chinese population. Mol Carcinog 50:863–870
Caputo F, Vegliante R, Ghibelli L (2012) Redox modulation of DNA damage response. Biochem Pharmacol 34:1292–1306
ChamperisTsaniras S, Kanellakis N, Symeonidou IE, Nikolopoulou P, Lygerou Z, Taraviras S (2014) Licensing of DNA replication, cancer, pluripotency and differentiation: an interlinked world? Semin Cell Dev Biol 30:174–180
Chen HH, Wang YC, Fann MJ (2006) Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol Cell Biol 26:2736–2745
Chen HH, Wong YH, Geneviere AM, Fann MJ (2007) CDK13/CDC2L5 interacts with L-type cyclins and regulates alternative splicing. Biochem Biophys Res Commun 354:735–740
Chen S, Xiong GS, Wu S, Mo J (2012) Downregulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 enhances the sensitivity of human pancreatic cancer cells to radiotherapy in vitro. Cancer Biother Radiopharm 28:169–176
Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF et al (1999) The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J 18:1571–1583
Choi W, Lee ES (2022) Therapeutic targeting of DNA damage response in cancer. Int J Mol Sci 23:1701
Choi S, Joo HK, Jeon BH (2016) Dynamic regulation of APE1?Ref1 as a therapeutic target protein. Chonnam Med J 52:75–80
Christmann M, Tomicic MT, Roos WP, Kaina B (2003) Mechanisms of human DNA repair: an update. Toxicology 193:3–34
Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204
Colombo SL, Palacios-Callender M, Frakich N, De Leon J, Schmitt CA, Boorn L et al (2010) Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. Proc Natl Acad Sci U SA 107:18868–18873
Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S, Moncada S (2011) Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci U S A 108:21069–21074
Comin-Anduix B, Boren J, Martinez S, Moro C, Centelles JJ, Trebukhina R et al (2001) The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Eur J Biochem 268:4177–4182
Cornell R, Grove GL, Rothblat GH, Horwitz AF (1977) Lipid requirement for cell cycling. The effect of selective inhibition of lipid synthesis. Exp Cell Res 109:299–307
Curtin NJ (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12:801–817
Cyr AR, Domann FE (2011) The redox basis of epigenetic modifications: from mechanisms to functional consequences. Antioxid Redox Signal 15:551–589
d’Adda di Fagagna F (2014) A direct role for small non-coding RNAs in DNA damage response. Trends Cell Biol 24:171–178
Dali-Youcef N, Mataki C, Coste A, Messaddeq N, Giroud S, Blanc S, Koehl C, Champy MF, Chambon P, Fajas L et al (2007) Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure. Proc Natl Acad Sci U S A 104:10703–10708
Darville MI, Rousseau GG (1997) E2F-dependent mitogenic stimulation of the splicing of transcripts from an S phase-regulated gene. Nucleic Acids Res 25:2759–2765
Darville MI, Antoine IV, Mertens-Strijthagen JR, Dupriez VJ, Rousseau GG (1995) An E2F-dependent late-serum-response promoter in a gene that controls glycolysis. Oncogene 11:1509–1517
DeBont R, van Larebeke N (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19:169–185
DeRosa V, Erkekoglu P, Forestier A, Favier A, Hincal F, Diamond AM, Douki T, Rachidi W (2012) Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCaP prostate cancer cells. Free Radic Res 46:105–115
Dianova II, Bohr VA, Dianov GL (2001) Interaction of human AP endonuclease 1 with flap endonuclease 1 and proliferating cell nuclear antigen involved in long-patch base excision repair. Biochemistry 40:12639–12644
Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M (2013) Targeting cell cycle regulation in cancer therapy. Parmaco Ther 138:255–271
Dijk M, Typas D, Mullenders L, Pines A (2014) Insight in the multilevel regulation of NER. Exp Cell Res 329:116–123
Dizdaroglu M (2012) Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett 327:26–47
Doetsch PW, Cunningham RP (1990) The enzymology of apurinic/apyrimidinic endonucleases. Mutat Res 236:173–201
Domingo-Sananes MR, Kapuy O, Hunt Y, Novak B (2011) Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis. Philos Trans R Soc B 366:3584–3594
Dominguez-Brauer C, Thu KL, Mason JM, Blaser H, Bray MR, Mak TW (2015) Targeting mitosis in cancer: emerging strategies. Mol Cell 60:524–536
Dong P, Maddali MV, Srimani JK, Thelot E, Navina JR, Mathey-Prevot B, You L (2014) Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control. Nat Commun 5:4750. 11 pages
Drosos Y, Escobar D, Chiang MY, Roys K, Valentine V et al (2017) ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer. Sci Rep 7:11144. 14 pages
Dunphy WG, Kumagai A (1991) The cdc25 protein contains an intrinsic phosphatase activity. Cell 67:189–196
Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463
Ema M, Hirota K, Mimura J, Abe H, Yodoi J, Sogawa K et al (1999) Molecular mechanisms of transcription activation by HLF and HIF1α in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J 18:1905–1914
Estevez-Garcia IO, Cordobo-Gonzalez V, Lara-Padilla E, Fuentes-Toledo A, Falfain-Valenda R, Campose-Rodriguez R, Abarca-Rojano E (2014) Glucose and glutamine metabolism control by APC and SCF during the G1-to –S phase transition of the cell cycle. J Physiol Biochem 70:569–581
Evans AR, Limp-Foster M, Kelley MR (2000) Going APE. Over ref-1. Mutat Res 461:83–108
Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS, Kelley MR (2008) 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
Fleck O, Nielsen O (2004) DNA repair. J Cell Sci 117:515–517
Francia S, Michelini F, Saxena A, Tang D, deHoon M et al (2012) Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488:231–235
Francia S, Cabrini M, Matti V, Oldani A, d’Adda di Fagagna F (2016) DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors. J Cell Sci 129:1468–1476
Fritz G, Kaina B (1999) Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1. Oncogene 18:1033–1040
Fruehauf JP, Meyskens FL (2007) Reactive oxygen species: a breath of life or death? Clin Cancer Res 13:789–794
Gabrielli B, Brooks K, Pavey S (2012) Defective cell cycle checkpoints as targets for anti-cancer therapies. Front Pharmacol 3:9. 6 pages
Gaiddon C, Moorthy NC, Prives C (1999) Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. EMBO J 18:5609–5621
Galluzzi L, Kepp O, Tajeddine N, Kroemer G (2008) Disruption of the hexokinase-VDAC complex for tumor therapy. Oncogene 27:4633–4635
Gao M, Wei W, Li MM, Wu YS, Ba Z et al (2014) Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination. Cell Res 24:532–541
Gavande NS, VanderVere-Carozza HHD, Jalal SI, Sears CR, Pawelczak KS, Turchi JJ (2016) DNA repair targeted therapy: the past or future of cancer treatment? Pharmaco Ther 160:65–83
Gederaas OA, Søgaard CD, Viset T, Bachke S, Bruheim P, Arum CJ, Otterlei M (2014) Increased anticancer efficacy of intravesical mitomycin C therapy when combined with a PCNA targeting peptide. Transl Oncol 7:812–823
Giola U, Francia S, Cabrini M, Brambillasca S, Michelini F, Jones-Weinert CW, Adda di Fagagna F (2019) Pharmacoligical boost of DNA damage response and repair by enhanced biogenesis of DNA damage response RNAs. Sci Rep 9:6460. 15 pages
Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132–138
Goldenson B, Crispino JD (2015) The aurora kinases in cell cycle and leukemia. Oncogene 34:537–545
Goto Y, Hayashi R, Kang D, Yoshida K (2006) Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells. J Cell Physiol 209:923–934
Graf F, Koehler L, Kniess T, Wuest F, Mosch B, Pietzsch J (2009) Cell cycle regulating kinase Cdk4 as a potential target for tumor cell treatment and tumor imaging. J Oncol 2009:106378
Grana X, Reddy EP (1995) Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11:211–219
Grollman AP, Moriya M (1993) Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet 9:246–249
Grösch S, Kaina B (1999) Transcriptional activation of apurinic/apyrimidinic endonuclease (ape, Ref-1) by oxidative stress requires CREB. Biochem Biophys Res Commun 261:859–863
Guetens G, De Boeck G, Highley M, van Oosterom AT, de Bruijn EA (2002) Oxidative DNA damage: biological significance and methods of analysis. Crit Rev Clin Lab Sci 39:331–457
Guo Z, Kozlov S, Lavin MF, Person MD, Paull TT (2010) ATM activation by oxidative stress. Science 330:517–521
Hajas G, Bacsi A, Aguilera-Aguirre L, Hegde M, Tapas KH et al (2013) Free radical biology and medicine 8-oxoguanine DNA glycosylase-1 links DNA repair to cellular signaling via the activation of the small GTPase Rac1. Free Radic Biol Med 61:384–394
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
Havens CG, Ho A, Yoshioka N, Dowdy SF (2006) Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species. Mol Cell Biol 26:4701–4711
Hegde ML, Hazra TK, Mitra S (2008) Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 18:27–47
Hegde ML, Mantha AK, Hazra TK, Bhakat KK, Mitra S, Szczesny B (2012) Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases. Mech Ageing Dev 133:157–168
Hegde ML, Hegde PM, Bellot LJ, Mandal SM, Hazra TK, Li GM, Boldogh I, Tomkinson AE, Mitra S (2013) Prereplicative repair of oxidized bases in the human genome is mediated by NEIL1 DNA glycosylase together with replication proteins. Proc Natl Acad Sci U S A 110:E3090–E3099
Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J (1997) 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
Hirota K, Murata M, Sachi Y, Nakamura H, Takeuchi J, Mori K, Yodoi J (1999) 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
Hoeferlin LA, Oleinik NV, Krupenko NI, Krupenko SA (2011) Activation of p21-dependent G1/G2 arrest in the absence of DNA damage as an antiapoptotic response to metabolic stress. Genes Cancer 2:889–899
Hoeijmakers JH (2001a) DNA repair mechanisms. Maturitas 38:17–22
Hoeijmakers JH (2001b) Genome maintenance mechanisms for preventing cancer. Nature 411:366–374
House NCM, Koch MR, Freudenreich CH (2014) Chromatin modifications and DNA repair: beyond double-strand breaks. Front Genet 5:296. 18 pages
Hromas R, Wray J, Lee SH, Martinez L, Farrington J, Corwin LK, Ramsey H, Nickoloff JA, Williamson EA (2008) 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
Hsieh MM, Hegde V, Kelley MR, Deutsch WA (2001) Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation. Nucleic Acids Res 29:3116–3122
Hsieh MC, Das D, Sambandam N, Zhang MQ, Nahle Z (2008) Regulation of the PDK4 isozyme by the Rb-E2F1 complex. J Biol Chem 283:27410–27417
Hussain SP, Amstad P, He P, Robles A, Lupold S, Kaneko I et al (2004) p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Cancer Res 64:2350–2356
Hwang JH, Hwang IS, Liu QH, Woo ER, Lee DG (2012) (+)-Medioresinol leads to intracellular ROS accumulation and mitochondria-mediated apoptotic cell death in Candida albicans. Biochimie 94:1784–1793
Inoguchi T, Sonta T, Tsubouchi H, Etoh T, Kakimoto M et al (2003) Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P) H oxidase. J Am Soc Nepherol 14:s227–s232
Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078
Jackson EB, Theriot CA, Chattopadhyay R, Mitra S, Izumi T (2005) Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1). Nucleic Acids Res 33:3303–3312
Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D (2011) Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Anticancer Res 31:379–385
Jena NR (2012) DNA damage by reactive species: mechanisms, mutation and repair. J Biosci 37:503–517
Jeon BH, Gupta G, Park YC, Qi B, Haile A, Khanday FA et al (2004) Apurinic/apyrimidinic endonuclease 1 regulates endothelial NO production and vascular tone. Circ Res 95:902–910
Jiang P, Du W, Wang X, Mancuso A, Gao X, Wu M et al (2011a) p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol 13:310–316
Jiang A, Gao H, Kelley MR, Qiao X (2011b) Inhibition of APE1/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo. Vis Res 51:93–100
Jiang X, Shan J, Dai N, Zhong Z, Qing Y, Yang Y et al (2015) Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma. Cancer Sci 106:1394–1401
Jiricny J (2006) The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 7:335–346
Jurkovicova D, Neophytou CM, Gasparovic AC, Goncalves AC (2022) DNA damage response in cancer therapy and resistance: challenges and opportunities. Int J Mol Sci 23:14672. 32 pages
Kaelin WG Jr (2009) Synthetic lethality: a framework for the development of wiser cancer therapeutics. Genome Med 1:99. 6 pages
Kaina B, Christmann M, Naumann S, Roos WP (2007) MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst) 6:1079–1099
Kalen AL, Sarsour EH, Venkataraman S, Goswami PC (2006) Mn-superoxide dismutase overexpression enhances G2 accumulation and radioresistance in human oral squamous carcinoma cells. Antioxid Redox Signal 8:1273–1281
Kalucka J, Missiaen R, Georgiadon M, Schoors S, Lange C, DeBock R, Dewerchin M, Carmeher P (2015) Metabolic control of the cell cycle. Cell Cycle 14:3379–3388
Kantidze OL, Velichko AK, Luzhin AV, Petrova NV, Razin SV (2018) Synthetically lethal interactions of ATM, ATR, and DNA-PKcs. Trends Cancer 4:755–768
Kastan MB, Bartek J (2004) Cell cycle checkpoints and cancer. Nature 432:316–323
Kelley MR, Fishel ML (2008) DNA repair proteins as molecular targets for cancer therapeutics. Anti Cancer Agents Med Chem 8:417–425
Kelley MR, Parsons SH (2001) Redox regulation of the DNA repair function of the human AP endonuclease Ape1/ref-1. Antioxid Redox Signal 3:671–683
Kelley MR, Logsdon D, Fishel M (2014) Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncol 10:1215–1237
Khan MA, Tania M, Zhang DZ, Chen HC (2010) Antioxidant enzymes and cancer. Clin J Cancer Res 22:87–92
Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–254
Khodyreva SN, Prasad R, Ilina ES, Sukhanova MV, Kutuzov MM, Liu Y et al (2010) Apurinic/apyrimidinic (AP) site recognition by the 5′-dRP/AP lyase in poly (ADP-ribose) polymerase-1 (PARP-1). Proc Natl Acad Sci U S A 107:22090–22095
Kim YJ, Wilson DM 3rd (2012) Overview of base excision repair biochemistry. Curr Mol Pharmacol 5:3–13
Kim CS, Son SJ, Kim EK, Kim SN, Yoo DG, Kim HS et al (2006) Apurinic/apyrimidinic endonuclease1/redox factor-1 inhibits monocyte adhesion in endothelial cells. Cardiovasc Res 69:520–526
King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646
Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5:773–785
Kroemer G, Pouyssegur J (2008) Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell 13:472–482
Kuhne M, Riballo E, Rief N, Rothkamm K, Jeggo PA, Lobrich M (2004) A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res 64:500–508
Lam MH, Liu Q, Elledge SJ, Rosen JM (2004) Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 6:45–59
Lambert S, Carr AM (2005) Checkpoint responses to replication fork barriers. Biochimie 87:591–602
Landis MW, Pawlyk BS, Li T, Sicinski P, Hinds PW (2006) Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9:13–22
Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N et al (2012) Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science 336:225–228
Lee DH, Liu Y, Lee HW, Xia B, Brice AR, Park SH, Balduf H, Dominy BN, Cao W (2015) A structural determinant in the uracil DNA glycosylase superfamily for the removal of uracil from adenine/uracil base pairs. Nucleic Acids Res 43:1081–1089
LeMaire-Adkins R, Radke K, Hunt PA (1997) Lack of checkpoient control at the metaphase/anaphase transition: a mechanism of meiotic nondisjunction in mammalian females. J Cell Biol 139:1611–1619
Lemons JM, Feng XJ, Bennett BD, Legesse-Miller A, Johnson EL, Raitman I, Pollina EA, Rabitz HA, Rabinowitz JD, Coller HA (2010) Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol 8:e1000514
Li M, Wilson DM 3rd (2014) Human apurinic/apyrimidinic endonuclease 1. Antioxid Redox Signal 20:678–707
Li D, Zhu Y, Tang Q, Lu H, Li H, Yang Y et al (2009) A new G6PD knockdown tumor-cell line with reduced proliferation and increased susceptibility to oxidative stress. Cancer Biother Radiopharm 24:81–90
Li M, Zhong Z, Zhu J, Xiang D, Dai N, Cao X et al (2010) Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1. J Biol Chem 285:14871–14881
Li MX, Shan JL, Wang D, He Y, Zhou Q, Xia L et al (2012) Human apurinic/apyrimidinic endonuclease 1 translocalizes to mitochondria after photodynamic therapy and protects cells from apoptosis. Cancer Sci 103:882–888
Liaudat AC, Bohl LP, de Talamoni NGT, Maletto B, Pistoresi-Palencia MC, Picotto G (2014) Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells. Anti-Cancer Drugs 25:810–818
Lieber MR (2010) NHEJ and its backup pathways in chromosomal translocations. Nat Struct Mol Biol 17:393–395
Lin CH, Chen PM, Cheng YW, Chen CY, Yuan CJ, Lee H (2012) The APE1 asp/asp genotype and the combination of APE1 asp/asp and hOGG1-Cys variants are associated with increased p53 mutation in non–small cell lung cancer. J Epidemiol 22:537–542
Lingappan K (2018) NF-kB in oxidative stress. Curr Opin Toxicol 7:81–86
Liu RH, Hotchkiss JH (1995) Potential genotoxicity of chronically elevated nitric oxide: a review. Mutat Res 339:73–89
Liu M, Wikonkal NM, Brash DE (1999) Induction of cyclin-dependent kinase inhibitors and G(1) prolongation by the chemopreventive agent N-acetylcysteine. Carcinogenesis 20:1869–1872
Lo YL, Jou YS, Hsiao CF, Chang GC, Tsai YH, Su WC et al (2009) A polymorphism in the APE1 gene promoter is associated with lung cancer risk. Cancer Epidemiol Biomark Prev 18:223–229
Loboda A, Stachurska A, Dorosz J, Zurawski M, Wegrzyn J, Kozakowska M, Jozkowicz A, Dulak J (2009) HIF-1 attenuates Ref-1 expression in endothelial cells: reversal by siRNA and inhibition of geranylgeranylation. Vasc Pharmacol 51:133–139
Lopez de Saro FJ, Marinus MG, Modrich P, O’Donnell M (2006) The beta sliding clamp binds to multiple sites within MutL and MutS. J Biol Chem 281:14340–14349
Lunt SY, Vander Heiden MG (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27:441–464
Luo M, He H, Kelley MR, Georgiadis MM (2010) Redox regulation of DNA repair: implications for human health and cancer therapeutic development. Antioxid Redox Signal 12:1247–1269
Luo M, Zhang J, He H, Su D, Chen Q, Gross ML et al (2012) Characterization of the redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease. Biochemistry 51:695–705
Maestre C, Delgado-Esteban M, Gomez-Sanchez JC, Bolanos JP, Almeida A (2008) Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity. EMBO J 27:2736–2745
Mahmoudi M, Azadmanesh K, Shokrgozar MA, Journeay WS, Laurent S (2011) Effect of nanoparticles on the cell life cycle. Chem Rev 111:3407–3432
Malumbres M (2011) Physiological relevance of cell cycle kinases. Physiol Rev 91:973–1007
Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1:222–231
Malumbres M, Barbacid M (2005) Mammalian cyclin-dependent kinases. Trends Biochem Sci 30:630–641
Malumbres M, Barbacid M (2007) Cell cycle kinases in cancer. Curr Opin Genet Dev 17:60–65
Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9:153–166
Malumbres M, Harlow E, Hunt T, Hunter T, Lahti JM, Manning G et al (2009) Cyclin-dependent kinases: a family portrait. Nat Cell Biol 11:1275–1276
Mandal S, Freije WA, Guptan P, Banerjee U (2010) Metabolic control of G1-S transition: cyclin E degradation by p53-induced activation of the ubiquitin-proteasome system. J Cell Biol 188:473–479
Mantha AK, Sarkar B, Tell G (2013) A short review on the implications of base excision repair pathway for neurons: relevance to neurodegenerative diseases. Mitochondrion 16:38–49
Martin A, Odajima J, Hunt SL, Dubus P, Ortega S, Malumbres M et al (2005) Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer Cell 7:591–598
Martinez MC, Post JA, Verkleij AJ, Verrips CT, Boonstra J (2001) The effect of hydrogen peroxide on the cyclin D expression in fibroblasts. Cell Mol Life Sci 58:990–996
Massague J (2004) G1 cell-cycle control and cancer. Nature 432:298–306
Mathupala SP, Ko YH, Pedersen PL (2006) Hexokinase II: cancer’s double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 25:4777–4786
Matsushima S, Kuroda J, Ago T, Zhai P, Park JY et al (2013) Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy. Circ Res 112:651–663
Matthews JR, Kaszubska W, Turcatti G, Wells TN, Hai RT (1993) Role of cysteine62 in DNA recognition by the p50 subunit of NF-kappa B. Nucleic Acids Res 21:1727–1734
Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA (2009) Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis 30:2–10
Medema RH, Kops GJ, Bos JL, Burgering BM (2000) AFX-like forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404:782–787
Meinhart A, Kamenski T, Hoeppner S, Baumli S, Cramer P (2005) A structural perspective of CTD function. Genes Dev 19:1401–1415
Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R et al (2011) Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci U S A 108:4394–4399
Menon SG, Sarsour EH, Kalen AL, Venkataraman S, Hitchler MJ, Domann FE, Oberley LW, Goswami PC (2007) Superoxide signaling mediates N-acetyl-L-cysteine-induced G1 arrest: regulatory role of cyclin D1 and manganese superoxide dismutase. Cancer Res 67:6392–6399
Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C et al (1992) A family of human cdc2-related protein kinases. EMBO J 11:2909–2917
Michelini F, Pitchiaya S, Vitelli V, Sharma S, Gioia U et al (2017) Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nat Cell Biol 19:1400–1411
Mikhed Y, Gorlach A, Knaus UG, Daiber A (2015) Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair. Redox Biol 5:275–289
Mitra K, Wunder C, Roysam B, Lin G, Lippincott-Schwartz J (2009) A hyperfused mitochondrial state achieved at G1–S regulates cyclin E buildup and entry into S phase. Proc Natl Acad Sci U S A 106:11960–11965
Molenaar JJ, Ebus ME, Koster J, van Sluis P, van Noesel CJ, Versteeg R et al (2008) Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma. Cancer Res 68:2599–2609
Montalto AS, Curro M, Russo T, Visalli G, Impellizzeri P, Antonuccio P, Arena S, Borruto FA, Scaffari G, Ientile R, Romeo C (2013) In vitro CO2-induced ROS production impaires cell cycle in SH-SY5Y neuroblastoma cells. Pediatr Surg Int 29:51–59
Montariello D, Troiano A, Di Girolamo D, Beneke S, Calabrò V, Quesada P (2015) Effect of poly(ADP-ribose) polymerase and DNA topoisomerase I inhibitors on the p53/p63-dependent survival of carcinoma cells. Biochem Pharmacol 94:212–219
Moreira JDV, Peres S, Steyaert JM, Bigan E, Pauleve L, Nogueira ML, Schwartz L (2015) Cell cycle progression is regulated by interwined redox oscillators. Theor Biol Med Model 12:10. 14 pages
Morgan DO (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 13:261–291
Motegi A, Masutani M, Yoshioka KI, Bessho T (2019) Aberrations in DNA repair pathways in cancer and therapeutic significances. Semin Cancer Biol 58:29–46
Moynahan ME, Jasin M (2010) Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 11:196–207
Muro Y, Sugiura K, Mimori T, Akiyama M (2015) DNA mismatch repair enzymes: genetic defects and autoimmunity. Clin Chim Acta 442:102–109
Narayanan S, Janakiraman B, Kumar L, Radhakrishnan SK (2015) A cell cycle-controlled redox switch regulates the topoisomerase IV activity. Genes Dev 29:1175–1187
Nelson DM, Ye X, Hall C, Santos H, Ma T, Kao GD, Yen TJ, Harper JW, Adams PD (2002) Coupling of DNA synthesis and histone synthesis in S phase independent of cyclin/cdk2 activity. Mol Cell Biol 22:7459–7472
Nicholson RI, Gee JMW, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37:9–15
Nurse P (2000) A long twentieth century of the cell cycle and beyond. Cell 100:71–78
O’Connor MJ (2015) Targeting the DNA damage response in cancer. Mol Cell 60:547–560
Odom RY, Dansby MY, Rollins-Hairston AM, Jackson KM, Kirlin WG (2009) Phytochemical induction of cell cycle arrest by glutathione oxidation and reversal by N-acetylcysteine in human colon carcinoma cells. Nutr Cancer 61:332–339
Okamoto T, Kohno M, Ito K, Takada K, Katsura M et al (2017) Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma. Anticancer Res 37:1729–1735
Opresko PL, Fan J, Danzy S, Wilson DM 3rd, Bohr VA (2005) Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic Acids Res 33:1230–1239
Orlando DA, Lin CY, Bernard A, Wang JY, Socolar JE, Iversen ES, Hartemink AJ, Haase SB (2008) Globel control of cell-cycle transcription by coupled CDK and network oscillators. Nature 453:944–947
Ozaki M, Suzuki S, Irani K (2002) Redox factor-1/APE suppresses oxidative stress by inhibiting the rac1 GTPase. FASEB J 16:889–890
Palancade B, Bensaude O (2003) Investigating RNA polymerase II carboxyl-terminal domain (CTD) phosphorylation. Eur J Biochem 270:3859–3870
Pardee AB (1974) A restriction point for control of normal animal cell proliferation. Proc Natl Acad Sci U S A 71:1286–1290
Park MS, Kim CS, Joo HK, Lee YR, Kang G, Kim SJ et al (2013) Cytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells. Mol Cells 36:439–445
Park JS, Kim HL, Kim YJ, Weon JI, Sung MK, Chung HW, Seo YR (2014) Human AP endonuclease 1: a potential marker for the prediction of environmental carcinogenesis risk. Oxidative Med Cell Longev 2014:730301. 15 pages
Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7:644–656
Pilie PG, Tang C, Mills GB, Yap TA (2019) State-of-the-art strategies for targeting the DNA damage response in cancer. Nat Rev Clin Oncol 16:81–104
Prelich G (2002) DNA polymerase II carboxy-terminal domain kinases: emerging clues to their function. Eukaryot Cell 1:153–162
Qi Y, Zhang Y, Baller JA, Voytas DF (2016) Histone H2AX and the small RNA pathway modulate both non-homologous end-joining and homologous recombination in plants. Mutat Res 783:9–14
Raffoul JJ, Banerjee S, Singh-Gupta V, Knoll Z, Fite A, Zhang H et al (2007) 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
Raffoul JJ, Heydari AR, Hillman GG (2012) DNA repair and cancer therapy: targeting APE1/Ref-1 using dietary agents. J Oncol 2012:370481. 11 pages
Ray D, Terao Y, Fuhrken PG, Ma ZQ, DeMayo FJ, Christov K et al (2007) Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. Cancer Res 67:984–991
Ray D, Terao Y, Christov K, Kaldis P, Kiyokawa H (2011) Cdk2-null mice are resistant to Erb-2-induced mammary tumorigenesis. Neoplasia 13:439–444
Robbins SL, Cotran RS (2004) In: Kumar V, Abbas AK, Fausto N (eds) Pathological basis of disease. Elsvier. ISBN 81-8143-528-3
Romeo Y, Zhang X, Roux PP (2012) Regulation and function of the RSK family of protein kinases. Biochem J 441:553–569
Rowe BP, Glazer PM (2010) Emergence of rationally designed therapeutic strategies for breast cancer targeting DNA repair mechanisms. Breast Cancer Res 12:203. 11 pages
Sakamaki T, Casimiro MC, Ju X, Quong AA, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y et al (2006) Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol 26:5449–5469
Santamaria D, Barriere C, Cerqueira A, Hunt S, Tardy C, Newton K et al (2007) Cdk1 is sufficient to drive the mammalian cell cycle. Nature 448:811–815
Satyanarayana AP, Kaldis P (2009) Mammalian cell-cycle regulation: several CDKs, numerous cyclins and diverse compensatory mechanisms. Oncogene 28:2925–2939
Sausville EA (2002) Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol Med 8:S32–S37
Savitsky PA, Finkel T (2002) Redox regulation of Cdc25C. J Biol Chem 277:20535–20540
Schmidt M, Fernandez de Mattos S, van der Horst A, Klompmaker R, Kops GJ, Lam EW, Burgering BM, Medema RH (2002) Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D. Mol Cell Biol 22:7842–7852
Sebastian B, Kakizuka A, Hunter T (1993) Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. Proc Natl Acad Sci U S A 90:3521–3524
Shan G, Li Y, Zhang J, Li W, Szulwach KE et al (2008) A small molecule enhances RNA interference and promotes microRNA processing. Nat Biotechnol 26:933–940
Shapiro GI (2006) Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 24:1770–1783
Sharma V, Collins LB, Clement JM, Zhang Z, Nakamura J, Swenberg JA (2014) Molecular dosimetry of endogenous and exogenous O(6)-methyl-dG and N7-methyl-G adducts following low dose [D3]-methylnitrosourea exposures in cultured human cells. Chem Res Toxicol 27:480–482
Sheaff RJ, Groudine M, Gordon M, Roberts JM, Clurman BE (1997) Cyclin E-CDK2 is a regulator of p27Kip1. Genes Dev 11:1464–1478
Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677
Sherr CJ, Roberts JM (1999) Positive and negative regulators of G1-phase progression. Genes Dev 13:1501–1512
Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18:2699–2711
Shiloh Y, Kastan MB (2001) ATM genome stability, neuronal development and cancer cross paths. Adv Cancer Res 83:209–254
Shiloh Y, Ziv Y (2013) The ATM protein kinase: regulating the cellular response to genotoxic stress, and more nature reviews. Mol Cell Biol 14:197–210
Sies H (1993) Strategies of antioxidant defense. Eur J Biochem 215:213–219
Singh P, Saxena R, Srinivas G, Pande G, Chattopadhyay A (2013) Cholesterol biosynthesis and homeostasis in regulation of the cell cycle. PLoS One 8:e58833
Slupphaug G, Kavli B, Krokan HE (2003) The interacting pathways for prevention and repair of oxidative DNA damage. Mutat Res 531:231–251
Smith JA, Martin L (1973) Do cell cycle? Proc Natl Acad Sci U S A 70:1263–1267
Song YJ, Lee JY, Joo HK, Kim HS, Lee SK, Lee KH et al (2008) Tat-APE1/ref-1 protein inhibits TNF-alpha-induced endothelial cell activation. Biochem Biophys Res Commun 368:68–73
Sousa E, Graca I, Baptista T, Vieira FQ, Palmeira C et al (2013) Enoxacin inhibits growth of prostate cancer cells and effectively restores microRNA processing. Epigenetics 8:548–558
Stracker TH, Petrini JH (2011) The MRE11 complex: starting from the ends nature reviews. Mol Cell Biol 12:90–103
Su D, Delaplane S, Luo M, Rempel DL, Vu B, Kelley MR et al (2011) Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: evidence for an alternate conformation of the enzyme. Biochemistry 50:82–92
Svegliati S, Marrone G, Pezone A, Spadoni T, Grieco A, Moroncini G, Grieco D, Vinciguerra M, Agnese S, Jungel A, Distler O, Musti AM, Gabrielli A, Avvedimento EV (2014) Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis. Sci Signal 7:ra84
Swahari V, Nakamura A, Baran-Gale J, Garcia I, Crowther AJ et al (2016) Essential function of Dicer in resolving DNA damage in the rapidly dividing cells of the developing and malignant. Cerebellum Cell Rep 14:216–224
Tchakarska G, Roussel M, Troussard X, Sola B (2011) Cyclin D1 inhibits mitochondrial activity in B cells. Cancer Res 71:1690–1699
Tell G, Zecca A, Pellizzari L, Spessotto P, Colombatti A, Kelley MR, Damante G, Pucillo C (2000) 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
Tell G, Crivellato E, Pines A, Paron I, Pucillo C, Manzini G et al (2001) Mitochondrial localization of APE/Ref-1 in thyroid cells. Mutat Res 485:143–152
Tell G, Damante G, Caldwell D, Kelley MR (2005) The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal 7:367–384
Tell G, Quadrifoglio F, Tiribelli C, Kelley MR (2009) The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal 11:601–619
Tetsu O, McCormick F (2003) Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 3:233–245
Thakur S, Sarkar B, Cholia RP, Gautam N, Dhiman M, Mantha AK (2014) APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions. Exp Mol Med 46:e106. 21 pages
Toledano MB, Leonard WJ (1991) Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro. Proc Natl Acad Sci U S A 88:4328–4332
Toledo LI, Altmeyer M, Rask MB, Lukas CL, Larsen DH et al (2013) ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 155:1088–1103
Tomaszowski KH, Aasland D, Margison GP, Williams E, Pinder SI, Modesti M, Fuchs RP, Kaina B (2015) The bacterial alkyltransferase-like (eATL) protein protects mammalian cells against methylating agent-induced toxicity. DNA Repair (Amst) 28:14–20
Tu BP, Kudlicki A, Rowicka M, McKnight SL (2005) Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science 310:1152–1158
Tubbs A, Nussenzweig A (2017) Endogenous DNA damage as a source of genomic instability in cancer. Cell 168:644–656
Tudek B, Winczura A, Janik T, Sjomek A, Foksinski M, Olinski R (2010) Involvement of oxidatively damage DNA and repair in cancer development and aging. Am J Transl Res 15:254–284
Tudzarova S, Colombo SL, Stoeber K, Carcamo S, Williams GH, Moncada S (2011) Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle. Proc Natl Acad Sci U S A 108:5278–5283
Turk PW, Laayoun A, Smith SS, Weitzman SA (1995) DNA adduct 8-hyroxyl-2′-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase. Carcinogenesis 16:1253–1255
Turowski PC, Franckhauser MC, Morris P, Vaglio A, Fernandez N, Lamb JC (2003) Functional Cdc25C dual-specificity phosphatase is required for S-phase entry in human cells. Mol Biol Cell 14:2984–2998
Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM, Morgan DO (2003) Targets of the cyclin-dependent kinase Cdk1. Nature 425:859–864
Ushijima T (2005) Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer 5:223–231
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and oxidative stress-induced cancer. Chem Biol Interact 160:1–40
Venkitaraman AR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108:171–182
Verbon EH, Post JA, Boonstra J (2012) The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene 511:1–6
Viallard JF, Lacombe F, Belloc F, Pellegrin JL, Reiffers J (2001) Molecular mechanisms controlling the cell cycle: fundamental aspects and implications for oncology. Cancer Radiother 5:109–129
Vidal AE, Boiteux S, Hickson ID, Radicella JP (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein–protein interactions. EMBO J 20:6530–6539
Vijayakumar S, Liu G, Rus IA, Yao S, Chen Y et al (2011) High-frequency canonical Wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/β-catenin target gene, CDC25A. Cancer Cell 19:601–612
Vodermaier HC (2004) APC/C and SCF: controlling each other and the cell cycle. Curr Biol 14:R787–R796
Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310
Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137:413–431
Walker LJ, Robson CN, Black E, Gillespie D, Hickson ID (1993) 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
Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM, Pestell RG (2006) Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Proc Natl Acad Sci U S A 103:11567–11572
Wang YT, Tzeng DW, Wang CY, Hong JY, Yang JL (2013) APE1/Ref1 prevents oxidative inactivation of ERK for G1-to-S progression following lead acetate exposure. Toxicology 305:120–129
Wei W, Yang Z, Tang CH, Liu L (2011) Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-DNA alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine. Carcinogenesis 32:973–977
Wei W, Ba Z, Gao M, Wu Y, Ma Y et al (2012) A role for small RNAs in DNA double-strand break repair. Cell 149:101–112
Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11:872–884
White MA, Rites L, Cohen BA (2009) A systematic screen for transcriptional regulators of the yeast cell cycle. Genetics 181:435–446
Wood RD, Mitchell M, Lindahl T (2005) Human DNA repair genes. Mutat Res 577:275–283
Wu L, Yee A, Liu L, Carbonaro-Hall D, Venkatesan N et al (1994) Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase. Oncogene 9:2089–2096
Xanthoudakis S, Miao GG, Curran T (1994) The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. Proc Natl Acad Sci U S A 91:23–27
Yacoub A, Kelley MR, Deutsch WA (1997) The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation. Cancer Res 57:5457–5459
Yamaura M, Mitsushita J, Furuta S, Kiniwa Y, Ashida A et al (2009) NADPH oxidase 4 contributes to transformation phenotype of melanoma cells by regulating G2-M cell cycle progression. Cancer Res 69:2647–2654
Yamawaki H, Berk BC (2005) Thioredoxin: a multifunctional antioxidant enzyme in kidney, heart and vessels. Curr Opin Nephrol Hypertens 14:149–153
Yan YB (2016) Creatine kinase in cell cycle regulation and cancer. Amino Acids 48:1775–1784
Yoo DG, Song YJ, Cho EJ, Lee SK, Park JB, Yu JH et al (2008) Alteration of APE1/ref-1 expression in non-small cell lung cancer: the implications of impaired extracellular superoxide dismutase and catalase antioxidant systems. Lung Cancer 60:277–284
Yousef MI, Hussien HM (2015) Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng. Food Chem Toxicol 78:17–25
Yu Q, Geng Y, Sicinski P (2001) Specific protection against breast cancers by cyclin D1 ablation. Nature 411:1017–1021
Yu Q, Sicinska E, Geng Y, Ahnstrom M, Zagozdzon A, Kong Y et al (2006) Requirement for CDK4 kinase function in breast cancer. Cancer Cell 9:23–32
Zaky A, Busso C, Izumi T, Chattopadhyay R, Bassiouny A, Mitra S et al (2008) 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
Zannini L, Delia D, Buscemi G (2014) CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol 6:442–457
Zanuy M, Ramos-Montoya A, Villacanas O, Canela N, Miranda A, Aguilar E et al (2012) Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle. Metabolomics 8:454–464
Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16:2–9
Zhang J, Cicero SA, Wang L, Romito-Digiacomo RR, Yang Y, Herru K (2008) Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Proc Natl Acad Sci U S A 105:8772–8777
Zou GM, Karikari C, Kabe Y, Handa H, Anders RA, Maitra A (2009) 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
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Bansal, M.P. (2023). Cell Cycle, DNA Damage Repair Systems, and Impact of Redox Regulation in Cancer. In: Redox Regulation and Therapeutic Approaches in Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-99-7342-2_8
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