Gandhi, V., Ayres, M., Halgren, R. G., Krett, N. L., Newman, R. A., & Rosen, S. T. (2001). 8-chloro-cAMP and 8-chloro-adenosine act by the same mechanism in multiple myeloma cells. *Cancer Research*, *61*(14), 5474-5479.

Garcin, E. B., Gon, S., Sullivan, M. R., Brunette, G. J., Cian, A. De, Concordet, J.-P., Giovannangeli, C., Dirks, W. G., Eberth, S., Bernstein, K. A., Prakash, R., Jasin, M., & Modesti, M. (2019). Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells. *PLOS Genetics*, *15*(10), e1008355. https://doi.org/10.1371/journal.pgen.1008355

Gautier Defossez Sandra Le Guyader-Peyrou Zoé Uhry Pascale Grosclaude Marc Colonna Emmanuelle Dantony Patricia Delafosse Florence Molinié Anne-Sophie Woronoff Anne-Marie Bouvier Nadine Bossard Laurent Remontet Alain Monnereau SOMMAIRE, A. (n.d.). *Volume 1-Tumeurs solides*.

Gavande, N. S., VanderVere-Carozza, P. S., Hinshaw, H. D., Jalal, S. I., Sears, C. R., Pawelczak, K. S., & Turchi, J. J. (2016). DNA repair targeted therapy: The past or future of cancer treatment? *Pharmacology & Therapeutics*, *160*, 65–83. https://doi.org/10.1016/j.pharmthera.2016.02.003

Gavet, O., & Pines, J. (2010). Progressive Activation of CyclinB1-Cdk1 Coordinates Entry to Mitosis. *Developmental Cell*, *18*(4), 533–543. https://doi.org/10.1016/j.devcel.2010.02.013

Ge, X. Q., & Blow, J. J. (2010). Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories. *Journal of Cell Biology*, *191*(7), 1285-1297. https://doi.org/10.1083/jcb.201007074

Gil, J., & Peters, G. (2006). Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. *Nature Reviews Molecular Cell Biology*, *7*(9), 667–677. https://doi.org/10.1038/nrm1987

Gilbert, D. M. (2001). Making Sense of Eukaryotic DNA Replication Origins. *Science*, *294*(5540), 96–100.
https://doi.org/10.1126/science.1061724

Gisselsson, D., Pettersson, L., Höglund, M., Heidenblad, M., Gorunova, L., Wiegant, J., Mertens, F., Dal Cin, P., Mitelman, F., & Mandahl, N. (2000). Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. *Proceedings of the National Academy of Sciences*, *97*(10), 5357–5362.
https://doi.org/10.1073/pnas.090013497

Glover, T. W., Berger, C., Coyle, J., & Echo, B. (1984). DNA polymerase ? inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. *Human Genetics*, *67*(2), 136–142.
https://doi.org/10.1007/BF00272988

Goldhirsch, A., Wood, W. C., Coates, A. S., Gelber, R. D., Thürlimann, B., & Senn, H.-J. (2011). Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. *Annals of Oncology*, *22*(8), 1736–1747. https://doi.org/10.1093/annonc/mdr304

Goldman, I. D., & Matherly, L. H. (1985). The cellular pharmacology of methotrexate. *Pharmacology & Therapeutics*, *28*(1), 77–102. https://doi.org/10.1016/0163-7258(85)90083-X

Gon, S., Napolitano, R., Rocha, W., Coulon, S., & Fuchs, R. P. (2011). Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in *Escherichia coli*. *Proceedings of the National Academy of Sciences*, *108*(48), 19311–19316.
https://doi.org/10.1073/pnas.1113664108

Gong, W., Zhang, X., Wu, J., Chen, L., Li, L., Sun, J., Lv, Y., Wei, X., Du, Y., Jin, H., & Dong, J. (2012). RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-
cell lung cancer: A meta-analysis. *Lung Cancer*, **75**(3), 374-380.

https://doi.org/10.1016/j.lungcan.2011.08.003

González-Prieto, R., Muñoz-Cabello, A. M., Cabello-Lobato, M. J., & Prado, F. (2013). Rad51 replication fork recruitment is required for DNA damage tolerance. *The EMBO Journal*, **32**(9), 1307-1321.

https://doi.org/10.1038/emboj.2013.73

Goodarzi, A. A., Block, W. D., & Lees-Miller, S. P. (2003). The role of ATM and ATR in DNA damage-induced cell cycle control. *Progress in Cell Cycle Research*, **5**, 393-411.

Goodman, M. F., & Woodgate, R. (2013). Translesion DNA Polymerases. *Cold Spring Harbor Perspectives in Biology*, **5**(10), a010363-a010363. https://doi.org/10.1101/cshperspect.a010363

Gorgoulis, V. G., Vassiliou, L.-V. F., Karakaidos, P., Zacharatos, P., Kotsinas, A., Liloglou, T., Venere, M., DiTullio, R. A., Kastrinakis, N. G., Levy, B., Kletsas, D., Yoneta, A., Herlyn, M., Kittas, C., & Halazonetis, T. D. (2005). Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. *Nature*, **434**(7035), 907-913. https://doi.org/10.1038/nature03485

Goto, H., Kasahara, K., & Inagaki, M. (2015). Novel Insights into Chk1 Regulation by Phosphorylation. *Cell Structure and Function*, **40**(1), 43-50. https://doi.org/10.1247/csf.14017

Greene, B. L., Kang, G., Cui, C., Bennati, M., Nocera, D. G., Drennan, C. L., & Stubbe, J. (2020).
Ribonucleotide Reductases: Structure, Chemistry, and Metabolism

Annual Review of Biochemistry, 89(1), 45-75. https://doi.org/10.1146/annurev-biochem-013118-111843

Grem, J. L., King, S. A., O'Dwyer, P. J., & Leyland-Jones, B. (1988). Biochemistry and clinical activity of N-(phosphonacetyl)-L-aspartate: a review. *Cancer Research*, **48**(16), 4441-4454.

Groth, A., Corpet, A., Cook, A. J. L., Roche, D., Bartek, J., Lukas, J., & Almouzni, G. (2007). Regulation of Replication Fork Progression Through Histone Supply and Demand. *Science*, **318**(5858), 1928-1931.

https://doi.org/10.1126/science.1148992

Guedj, M., Marisa, L., de Reynies, A., Orsetti, B., Schiappa, R., Bibeau, F., MacGrogan, G., Lerebours, F., Finetti, P., Longy, M., Bertheau, P., Bertrand, F., Bonnet, F., Martin, A. L., Feugeas, J. P., Bièche, I., Lehmann-Che, J., Lidereau, R., Birnbaum, D., ... Theillet, C. (2012). A refined molecular taxonomy of breast cancer. *Oncogene*, **31**(9), 1196-1206. https://doi.org/10.1038/onc.2011.301

Guilliam, T., & Doherty, A. (2017). PrimPol—Prime Time to Reprime. *Genes*, **8**(1), 20.

https://doi.org/10.3390/genes8010020

Guittet, O., Håkansson, P., Voevodskaya, N., Fridd, S., Gräslund, A., Arakawa, H., Nakamura, Y., & Thelander, L. (2001). Mammalian p53R2 Protein Forms an Active Ribonucleotide Reductase in Vitro with the R1 Protein, Which Is Expressed Both in Resting Cells in Response to DNA Damage and in Proliferating Cells. *Journal of Biological Chemistry*, **276**(44), 40647-40651.

https://doi.org/10.1074/jbc.M106088200

Guo, Z., Kumagai, A., Wang, S. X., & Dunphy, W. G. (2000). Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in *Xenopus* egg extracts. *Genes & Development*, **14**(21), 2745-2756. https://doi.org/10.1101/gad.842500

Haahr, P., Hoffmann, S., Tollenaere, M. A. X., Ho, T., Toledo, L. I., Mann, M., Bekker-Jensen, S., Räschle, M., & Mailand, N. (2016). Activation of the ATR kinase by the RPA-binding protein ETAA1. *Nature Cell*

*Biology*, **18**(11), 1196-1207. https://doi.org/10.1038/ncb3422
Haggard, H. W., & Smith, G. M. (n.d.). JOHANNES MULLER AND THE MODERN CONCEPTION OF CANCER*. In *YALB JOURNAL OF BIOLOGY AND MEDICINE* (Vol. 10, Issue 5).

Håkansson, P., Hofer, A., & Thelander, L. (2006). Regulation of Mammalian Ribonucleotide Reduction and dNTP Pools after DNA Damage and in Resting Cells. *Journal of Biological Chemistry, 281*(12), 7834–7841. https://doi.org/10.1074/jbc.M512894200

Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (n.d.). *An Oncogene-Induced DNA Damage Model for Cancer Development*. www.sciencemag.org

Hamperl, S., Bocek, M. J., Saldivar, J. C., Swigut, T., & Cimprich, K. A. (2017). Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses. *Cell, 170*(4), 774-786.e19. https://doi.org/10.1016/j.cell.2017.07.043

Han, X., Tang, J., Wang, J., Ren, F., Zheng, J., Gragg, M., Kiser, P., Park, P. S. H., Palczewski, K., Yao, X., & Zhang, Y. (2016). Conformational Change of Human Checkpoint Kinase 1 (Chk1) Induced by DNA Damage. *Journal of Biological Chemistry, 291*(25), 12951–12959.
https://doi.org/10.1074/jbc.M115.713248

Hanahan, D. (2022). Hallmarks of Cancer: New Dimensions. In *Cancer Discovery* (Vol. 12, Issue 1, pp. 31–46). American Association for Cancer Research Inc. https://doi.org/10.1158/2159-8290.CD-21-1059

Hanahan, D., & Weinberg, R. A. (2000). The Hallmarks of Cancer. *Cell, 100*(1), 57–70.
https://doi.org/10.1016/S0092-8674(00)81683-9

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of Cancer: The Next Generation. *Cell, 144*(5), 646–674.
https://doi.org/10.1016/j.cell.2011.02.013

Harbour, J. W., Luo, R. X., Santi, A. D., Postigo, A. A., & Dean, D. C. (1999). Cdk Phosphorylation Triggers Sequential Intramolecular Interactions that Progressively Block Rb Functions as Cells Move through G1. *Cell, 98*(6), 859–869. https://doi.org/10.1016/S0092-8674(00)81519-6

Harder, H. C., & Rosenberg, B. (1970). Inhibitory effects of anti-tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cellsin vitro. *International Journal of Cancer, 6*(2), 207–216.
https://doi.org/10.1002/ijc.2910060207

Harper, J. V., Anderson, J. A., & O'Neill, P. (2010). Radiation induced DNA DSBs: Contribution from stalled replication forks? *DNA Repair, 9*(8), 907–913. https://doi.org/10.1016/j.dnarep.2010.06.002

Hashimoto, Y., Chaudhuri, A. R., Lopes, M., & Costanzo, V. (2010). Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. *Nature Structural and Molecular Biology, 17*(11), 1305–1311. https://doi.org/10.1038/nsmb.1927

Hashimoto, Y., Puddu, F., & Costanzo, V. (2012). RAD51- and MRE11-dependent reassembly of uncoupled CMG helicase complex at collapsed replication forks. *Nature Structural & Molecular Biology, 19*(1), 17–24. https://doi.org/10.1038/nsmb.2177

Hawryłkiewicz, A., & Ptaszyńska, N. (2021). Gemcitabine peptide-based conjugates and their application in targeted tumor therapy. In *Molecules* (Vol. 26, Issue 2). MDPI AG.
https://doi.org/10.3390/molecules26020364

HEIDELBERGER, C., CHAUDHURI, N. K., DANNEBERG, P., MOOREN, D., GRIESBACH, L., DUSCHINSKY, R., SCHNITZER, R. J., PLEVEN, E., & SCHEINER, J. (1957). Fluorinated Pyrimidines, A New Class of Tumour-Inhibitory Compounds. *Nature, 179*(4561), 663–666. https://doi.org/10.1038/179663a0
Heinemann, V., Xu, Y. Z., Chubb, S., Sen, A., Hertel, L. W., Grindey, G. B., & Plunkett, W. (1992a). Cellular elimination of 2',2'-difluorodeoxycytidine 5'-triphosphate: a mechanism of self-potentiation. *Cancer Research*, **52**(3), 533–539.

Helmrich, A., Ballarino, M., & Tora, L. (2011). Collisions between Replication and Transcription Complexes Cause Common Fragile Site Instability at the Longest Human Genes. *Molecular Cell*, **44**(6), 966–977.
https://doi.org/10.1016/j.molcel.2011.10.013

Hills, S. A., & Diffley, J. F. X. (2014). DNA replication and oncogene-induced replicative stress. In *Current Biology* (Vol. 24, Issue 10). Cell Press. https://doi.org/10.1016/j.cub.2014.04.012

Hilton, B. A., Li, Z., Musich, P. R., Wang, H., Cartwright, B. M., Serrano, M., Zhou, X. Z., Lu, K. P., & Zou, Y. (2015). ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1. *Molecular Cell*, **60**(1), 35–46. https://doi.org/10.1016/j.molcel.2015.08.008

Hofer, A., Crona, M., Logan, D. T., & Sjöberg, B.-M. (2012). DNA building blocks: keeping control of manufacture. *Critical Reviews in Biochemistry and Molecular Biology*, **47**(1), 50–63.
https://doi.org/10.3109/10409238.2011.630372

Houghton, J. A., Tillman, D. M., & Harwood, F. G. (1995). Ratio of 2'-deoxyadenosine-5'-triphosphate/thymidine-5'-triphosphate influences the commitment of human colon carcinoma cells to thymineless death. *Clinical Cancer Research : An Official Journal of the American Association for Cancer Research*, **1**(7), 723–730.

Huang, Z., Hankinson, S. E., Colditz, G. A., Stampfer, M. J., Hunter, D. J., Manson, J. E., Hennekens, C. H., Rosner, B., Speizer, F. E., & Willett, W. C. (1997). Dual Effects of Weight and Weight Gain on Breast Cancer Risk. *JAMA*, **278*(17), 1407. https://doi.org/10.1001/jama.1997.03550170037029

Huff, S. E., Winter, J. M., & Dealwis, C. G. (2022). Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present. In *Biomolecules* (Vol. 12, Issue 6). MDPI. https://doi.org/10.3390/biom12060815

Huppert, J. L., & Balasubramanian, S. (2007). G-quadruplexes in promoters throughout the human genome. *Nucleic Acids Research*, **35**(2), 406–413. https://doi.org/10.1093/nar/gkl1057

Hurta, R. A., & Wright, J. A. (1992). Alterations in the activity and regulation of mammalian ribonucleotide reductase by chlorambucil, a DNA damaging agent. *The Journal of Biological Chemistry*, **267**(10), 7066–7071.

Isono, M., Niimi, A., Oike, T., Hagiwara, Y., Sato, H., Sekine, R., Yoshida, Y., Isobe, S.-Y., Obuse, C., Nishi, R., Petricci, E., Nakada, S., Nakano, T., & Shibata, A. (2017). BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation. *Cell Reports*, **18**(2), 520–532.
https://doi.org/10.1016/j.celrep.2016.12.042

Iyer, D., & Rhind, N. (2017a). The Intra-S Checkpoint Responses to DNA Damage. *Genes*, **8**(2), 74.
https://doi.org/10.3390/genes8020074

Iyer, D., & Rhind, N. (2017b). The Intra-S Checkpoint Responses to DNA Damage. *Genes*, **8**(2), 74.
https://doi.org/10.3390/genes8020074

Jain, R., Aggarwal, A. K., & Rechkoblit, O. (2018). Eukaryotic DNA polymerases. *Current Opinion in Structural Biology*, **53**, 77–87. https://doi.org/10.1016/j.sbi.2018.06.003

Jardim, M. J., Wang, Q., Furumai, R., Wakeman, T., Goodman, B. K., & Wang, X.-F. (2009). Reduced ATR or Chk1 Expression Leads to Chromosome Instability and Chemosensitization of Mismatch Repair–
deficient Colorectal Cancer Cells. *Molecular Biology of the Cell*, 20(17), 3801–3809.
https://doi.org/10.1091/mbc.e09-04-0303

Jenuwein, T., & Allis, C. D. (2001). Translating the Histone Code. *Science*, 293(5532), 1074–1080.
https://doi.org/10.1126/science.1063127

Jin, J., Shirogane, T., Xu, L., Nalepa, G., Qin, J., Elledge, S. J., & Harper, J. W. (2003). SCF β-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. *Genes & Development*, 17(24), 3062–3074.
https://doi.org/10.1101/gad.1157503

Johansson, E., Hjortsberg, K., & Thelander, L. (1998). Two YY-1-binding Proximal Elements Regulate the Promoter Strength of the TATA-less Mouse Ribonucleotide Reductase R1 Gene. *Journal of Biological Chemistry*, 273(45), 29816–29821.
https://doi.org/10.1074/jbc.273.45.29816

John, P. C. L., Mews, M., & Moore, R. (2001). Cyclin/cdk complexes: Their involvement in cell cycle progression and mitotic division. *Protoplasma*, 216(3–4), 119–142.
https://doi.org/10.1007/BF02673865

Jones, D. D. (1974). Oncogene Theory. *Science*, 184(4139), 853–853.
https://doi.org/10.1126/science.184.4139.853

Jones, R. M., Mortusewicz, O., Afzal, I., Lorvellec, M., García, P., Helleday, T., & Petermann, E. (2013). Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. *Oncogene*, 32(32), 3744–3753.
https://doi.org/10.1038/onc.2012.387

Jones, R. M., & Petermann, E. (2012). Replication fork dynamics and the DNA damage response. *Biochemical Journal*, 443(1), 13–26.
https://doi.org/10.1042/BJ20112100

Jossé, R., Martin, S. E., Guha, R., Ormanoglu, P., Pfister, T. D., Reaper, P. M., Barnes, C. S., Jones, J., Charlton, P., Pollard, J. R., Morris, J., Doroshow, J. H., & Pommier, Y. (2014). ATR Inhibitors VE-821 and VX-970 Sensitize Cancer Cells to Topoisomerase I Inhibitors by Disabling DNA Replication Initiation and Fork Elongation Responses. *Cancer Research*, 74(23), 6968–6979.
https://doi.org/10.1158/0008-5472.CAN-13-3369

Jossen, R., & Bermejo, R. (2013). The DNA damage checkpoint response to replication stress: A game of forks. In *Frontiers in Genetics* (Vol. 4, Issue MAR). https://doi.org/10.3389/fgene.2013.00026

Ju, B.-G., Lunyak, V. V., Perissi, V., Garcia-Bassets, I., Rose, D. W., Glass, C. K., & Rosenfeld, M. G. (2006). A Topoisomerase IIβ-Mediated dsDNA Break Required for Regulated Transcription. *Science*, 312(5781), 1798–1802.
https://doi.org/10.1126/science.1127196

Kamińska, M., Ciszewski, T., Łopacka-Szatan, K., Miotła, P., & Starosławska, E. (2015). Breast cancer risk factors. In *Przeglad Menopauzalny* (Vol. 14, Issue 3, pp. 196–202). Termedia Publishing House Ltd.
https://doi.org/10.5114/pm.2015.54346

Karlsson-Rosenthal, C., & Millar, J. B. A. (2006). Cdc25: mechanisms of checkpoint inhibition and recovery. *Trends in Cell Biology*, 16(6), 285–292.
https://doi.org/10.1016/j.tcb.2006.04.002

Karnani, N., & Dutta, A. (2011). The effect of the intra-S-phase checkpoint on origins of replication in human cells. *Genes & Development*, 25(6), 621–633.
https://doi.org/10.1101/gad.2029711

Kasahara, K., Goto, H., Enomoto, M., Tomono, Y., Kiyono, T., & Inagaki, M. (2010). 14-3-3γ mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. *The EMBO Journal*, 29(16), 2802–2812.
https://doi.org/10.1038/emboj.2010.157
Kaushal, S., & Freudenreich, C. H. (2019). The role of fork stalling and DNA structures in causing chromosome fragility. *Genes, Chromosomes and Cancer, 58*(5), 270-283.
https://doi.org/10.1002/gcc.22721

Keegan, K. S., Holtzman, D. A., Plug, A. W., Christenson, E. R., Brainerd, E. E., Flaggs, G., Bentley, N. J., Taylor, E. M., Meyn, M. S., Moss, S. B., Carr, A. M., Ashley, T., & Hoekstra, M. F. (1996). The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes. *Genes & Development, 10*(19), 2423-2437. https://doi.org/10.1101/gad.10.19.2423

Keith, C. T., & Schreiber, S. L. (1995). PIK-Related Kinases: DNA Repair, Recombination, and Cell Cycle Checkpoints. *Science, 270*(5233), 50-50. https://doi.org/10.1126/science.270.5233.50

Khanna, K. K., & Jackson, S. P. (2001). DNA double-strand breaks: signaling, repair and the cancer connection. *Nature Genetics, 27*(3), 247-254. https://doi.org/10.1038/85798

Kim, C. G., Ahn, J. B., Jung, M., Beom, S. H., Kim, C., Kim, J. H., Heo, S. J., Park, H. S., Kim, J. H., Kim, N. K., Min, B. S., Kim, H., Koom, W. S., & Shin, S. J. (2016). Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers. *British Journal of Cancer, 115*(1), 25-33.
https://doi.org/10.1038/bjc.2016.161

Kim, W. Y., & Sharpless, N. E. (2006). The Regulation of INK4/ARF in Cancer and Aging. *Cell, 127*(2), 265-275. https://doi.org/10.1016/j.cell.2006.10.003

Kinzler, K. W., & Vogelstein, B. (1997). Gatekeepers and caretakers. *Nature, 386*(6627), 761-763.
https://doi.org/10.1038/386761a0

Knott, S. R. V., Viggiani, C. J., & Aparicio, O. M. (2009a). To promote and protect: Coordinating DNA replication and transcription for genome stability. *Epigenetics, 4*(6), 362-365.
https://doi.org/10.4161/epi.4.6.9712

Knudson, A. G. (1971). Mutation and Cancer: Statistical Study of Retinoblastoma. *Proceedings of the National Academy of Sciences, 68*(4), 820-823. https://doi.org/10.1073/pnas.68.4.820

Köberle, B., Masters, J. R. W., Hartley, J. A., & Wood, R. D. (1999). Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. *Current Biology, 9*(5), 273-278. https://doi.org/10.1016/S0960-9822(99)80118-3

Kohnken, R., Kodigepalli, K. M., & Wu, L. (2015a). Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications. *Molecular Cancer, 14*(1), 176.
https://doi.org/10.1186/s12943-015-0446-6

Kolinjivadi, A. M., Sannino, V., de Antoni, A., Técher, H., Baldi, G., & Costanzo, V. (2017). Moonlighting at replication forks – a new life for homologous recombination proteins BRCA1, BRCA2 and RAD51. In *FEBS Letters* (Vol. 591, Issue 8, pp. 1083-1100). Wiley Blackwell. https://doi.org/10.1002/1873-3468.12556

Kotsantis, P., Petermann, E., & Boulton, S. J. (2018). Mechanisms of oncogene-induced replication stress: Jigsaw falling into place. In *Cancer Discovery* (Vol. 8, Issue 5, pp. 537-555). American Association for Cancer Research Inc. https://doi.org/10.1158/2159-8290.CD-17-1461

Koundrioukoff, S., Carignon, S., Técher, H., Letessier, A., Brison, O., & Debatisse, M. (2013). Stepwise Activation of the ATR Signaling Pathway upon Increasing Replication Stress Impacts Fragile Site Integrity. *PLoS Genetics, 9*(7), e1003643. https://doi.org/10.1371/journal.pgen.1003643
Kumagai, A., Kim, S.-M., & Dunphy, W. G. (2004). Claspin and the Activated Form of ATR-ATRIP Collaborate in the Activation of Chk1. *Journal of Biological Chemistry*, 279(48), 49599–49608.
https://doi.org/10.1074/jbc.M408353200

Kumagai, A., Lee, J., Yoo, H. Y., & Dunphy, W. G. (2006). TopBP1 Activates the ATR-ATRIP Complex. *Cell*, 124(5), 943–955. https://doi.org/10.1016/j.cell.2005.12.041

Kuzminov, A. (2001). Single-strand interruptions in replicating chromosomes cause double-strand breaks. *Proceedings of the National Academy of Sciences*, 98(15), 8241–8246.
https://doi.org/10.1073/pnas.131009198

Lahmann, P. H., Hoffmann, K., Allen, N., Van Gils, C. H., Khaw, K. T., Tehard, B., Berrino, F., Tjønneland, A., Bigaard, J., Olsen, A., Overvad, K., Clavel-Chapelon, F., Nagel, G., Boeing, H., Trichopoulos, D., Economou, G., Bellos, G., Palli, D., Tumino, R., ... Riboli, E. (2004). Body size and breast cancer risk: Findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). *International Journal of Cancer*, 111(5), 762–771. https://doi.org/10.1002/ijc.20315

Lam, M. H., Liu, Q., Elledge, S. J., & Rosen, J. M. (n.d.). *Chk1 is haploinsufficient for multiple functions critical to tumor suppression*.

Lambert, S., & Carr, A. M. (2013a). Impediments to replication fork movement: stabilisation, reactivation and genome instability. *Chromosoma*, 122(1–2), 33–45. https://doi.org/10.1007/s00412-013-0398-9

Lambert, S., & Carr, A. M. (2013b). Replication stress and genome rearrangements: lessons from yeast models. *Current Opinion in Genetics & Development*, 23(2), 132–139.
https://doi.org/10.1016/j.gde.2012.11.009

LAMBERT, S., FROGET, B., & CARR, A. (2007). Arrested replication fork processing: Interplay between checkpoints and recombination. *DNA Repair*, 6(7), 1042–1061.
https://doi.org/10.1016/j.dnarep.2007.02.024

Lambert, S., Mizuno, K., Blaisonneau, J., Martineau, S., Chanet, R., Fréon, K., Murray, J. M., Carr, A. M., & Baldacci, G. (2010). Homologous Recombination Restarts Blocked Replication Forks at the Expense of Genome Rearrangements by Template Exchange. *Molecular Cell*, 39(3), 346–359.
https://doi.org/10.1016/j.molcel.2010.07.015

Lambert, S., Watson, A., Sheedy, D. M., Martin, B., & Carr, A. M. (2005). Gross Chromosomal Rearrangements and Elevated Recombination at an Inducible Site-Specific Replication Fork Barrier. *Cell*, 121(5), 689–702. https://doi.org/10.1016/j.cell.2005.03.022

Lane, A. N., & Fan, T. W. M. (2015). Regulation of mammalian nucleotide metabolism and biosynthesis. In *Nucleic Acids Research* (Vol. 43, Issue 4, pp. 2466–2485). Oxford University Press.
https://doi.org/10.1093/nar/gkv047

Lassmann, G., Thelander, L., & Gräslund, A. (1992). EPR stopped-flow studies of the reaction of the tyrosyl radical of protein r2 from ribonucleotide reductase with hydroxyurea. *Biochemical and Biophysical Research Communications*, 188(2), 879–887. https://doi.org/10.1016/0006-291X(92)91138-G

Le Tallec, B., Koundrioukoff, S., Wilhelm, T., Letessier, A., Brison, O., & Debatisse, M. (2014). Updating the mechanisms of common fragile site instability: how to reconcile the different views? *Cellular and Molecular Life Sciences*, 71(23), 4489–4494. https://doi.org/10.1007/s00018-014-1720-2

Lederman, M. (1981). *Radarramon Oncdo~y Bwl Ph.v.r Vol 7*.
Lee, J., & Dunphy, W. G. (2013). The Mre11-Rad50-Nbs1 (MRN) complex has a specific role in the activation of Chk1 in response to stalled replication forks. *Molecular Biology of the Cell*, **24**(9), 1343–1353. https://doi.org/10.1091/mbc.e13-01-0025

Lee, J., Kumagai, A., & Dunphy, W. G. (2001). Positive Regulation of Wee1 by Chk1 and 14-3-3 Proteins. *Molecular Biology of the Cell*, **12**(3), 551–563. https://doi.org/10.1091/mbc.12.3.551

Lee, Y.-C., Zhou, Q., Chen, J., & Yuan, J. (2016). RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response. *Current Biology*, **26**(24), 3257–3268.
https://doi.org/10.1016/j.cub.2016.10.030

Lemaçon, D., Jackson, J., Quinet, A., Brickner, J. R., Li, S., Yazinski, S., You, Z., Ira, G., Zou, L., Mosammaparast, N., & Vindigni, A. (2017). MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. *Nature Communications*, **8**(1), 860.
https://doi.org/10.1038/s41467-017-01180-5

Leonard, A. C., & Mechali, M. (2013). DNA Replication Origins. *Cold Spring Harbor Perspectives in Biology*, **5**(10), a010116–a010116. https://doi.org/10.1101/cshperspect.a010116

Leppard, J. B., & Champoux, J. J. (2005). Human DNA topoisomerase I: relaxation, roles, and damage control. *Chromosoma*, **114**(2), 75–85. https://doi.org/10.1007/s00412-005-0345-5

Le Tallec, B., Millot, G. A., Blin, M. E., Brison, O., Dutrillaux, B., & Debatisse, M. (2013). Common Fragile Site Profiling in Epithelial and Erythroid Cells Reveals that Most Recurrent Cancer Deletions Lie in Fragile Sites Hosting Large Genes. *Cell Reports*, **4**(3), 420–428. https://doi.org/10.1016/j.celrep.2013.07.003

Letessier, A., Millot, G. A., Koundrioukoff, S., Lachagès, A.-M., Vogt, N., Hansen, R. S., Malfoy, B., Brison, O., & Debatisse, M. (2011). Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site. *Nature*, **470**(7332), 120–123. https://doi.org/10.1038/nature09745

Li, X., & Manley, J. L. (2005). Inactivation of the SR Protein Splicing Factor ASF/SF2 Results in Genomic Instability. *Cell*, **122**(3), 365–378. https://doi.org/10.1016/j.cell.2005.06.008

Li, Y., Zhang, H., Merkher, Y., Chen, L., Liu, N., Leonov, S., & Chen, Y. (2022). Recent advances in therapeutic strategies for triple-negative breast cancer. In *Journal of Hematology and Oncology* (Vol. 15, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13045-022-01341-0

Liao, S., Tammaro, M., & Yan, H. (2016). The structure of ends determines the pathway choice and Mre11 nuclease dependency of DNA double-strand break repair. *Nucleic Acids Research*, **44**(12), 5689–5701.
https://doi.org/10.1093/nar/gkw274

LIMA-DE-FARIA, A., & JAWORSKA, H. (1968). Late DNA Synthesis in Heterochromatin. *Nature*, **217**(5124), 138–142. https://doi.org/10.1038/217138a0

Limbo, O., Porter-Goff, M. E., Rhind, N., & Russell, P. (2011). Mre11 Nuclease Activity and Ctp1 Regulate Chk1 Activation by Rad3<sup>ATR</sup> and Tel1<sup>ATM</sup> Checkpoint Kinases at Double-Strand Breaks. *Molecular and Cellular Biology*, **31**(3), 573–583. https://doi.org/10.1128/MCB.00994-10

Lin, Y.-L., & Pasero, P. (2012). Interference Between DNA Replication and Transcription as a Cause of Genomic Instability. *Current Genomics*, **13**(1), 65–73. https://doi.org/10.2174/138920212799034767

Liu, H., Takeda, S., Kumar, R., Westergard, T. D., Brown, E. J., Pandita, T. K., Cheng, E. H.-Y., & Hsieh, J. J.-D. (2010). Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint. *Nature*, **467**(7313), 343–346. https://doi.org/10.1038/nature09350
Liu, Q., Guntuku, S., Cui, X. S., Matsuoka, S., Cortez, D., Tamai, K., Luo, G., Carattini-Rivera, S., DeMayo, F., Bradley, A., Donehower, L. A., & Elledge, S. J. (2000). Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. *Genes & Development*, *14*(12), 1448–1459.

Liu, S., Ho, C. K., Ouyang, J., & Zou, L. (2013). Nek1 kinase associates with ATR-ATRIP and primes ATR for efficient DNA damage signaling. *Proceedings of the National Academy of Sciences*, *110*(6), 2175–2180. https://doi.org/10.1073/pnas.1217781110

Liu, S., Opiyo, S. O., Manthey, K., Glanzer, J. G., Ashley, A. K., Amerin, C., Troksa, K., Shrivastav, M., Nickoloff, J. A., & Oakley, G. G. (2012). Distinct roles for DNA-PK, ATM and ATR in RPA phosphorylation and checkpoint activation in response to replication stress. *Nucleic Acids Research*, *40*(21), 10780–10794. https://doi.org/10.1093/nar/gks849

Liu, S., Shiotani, B., Lahiri, M., Maréchal, A., Tse, A., Leung, C. C. Y., Glover, J. N. M., Yang, X. H., & Zou, L. (2011). ATR Autophosphorylation as a Molecular Switch for Checkpoint Activation. *Molecular Cell*, *43*(2), 192–202. https://doi.org/10.1016/j.molcel.2011.06.019

Lolli, M. L., Sainas, S., Pippione, A. C., Giorgis, M., Boschi, D., & Dosio, F. (2018). Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy. *Recent Patents on Anti-Cancer Drug Discovery*, *13*(1). https://doi.org/10.2174/1574892812666171108124218

Lopes, M., Foiani, M., & Sogo, J. M. (2006). Multiple Mechanisms Control Chromosome Integrity after Replication Fork Uncoupling and Restart at Irreparable UV Lesions. *Molecular Cell*, *21*(1), 15–27. https://doi.org/10.1016/j.molcel.2005.11.015

López-Contreras, A. J., Gutierrez-Martinez, P., Specks, J., Rodrigo-Perez, S., & Fernandez-Capetillo, O. (2012). An extra allele of Chk1 limits oncogene-induced replicative stress and promotes transformation. *Journal of Experimental Medicine*, *209*(3), 455–461. https://doi.org/10.1084/jem.20112147

Lord, C. J., & Ashworth, A. (2016). BRCAness revisited. *Nature Reviews Cancer*, *16*(2), 110–120. https://doi.org/10.1038/nrc.2015.21

Lossaint, G., Larroque, M., Ribeyre, C., Bec, N., Larroque, C., Décaillet, C., Gari, K., & Constantinou, A. (2013). FANCD2 Binds MCM Proteins and Controls Replisome Function upon Activation of S Phase Checkpoint Signaling. *Molecular Cell*, *51*(5), 678–690. https://doi.org/10.1016/j.molcel.2013.07.023

Lukong, K. E. (2017). Understanding breast cancer – The long and winding road. In *BBA Clinical* (Vol. 7, pp. 64–77). Elsevier B.V. https://doi.org/10.1016/j.bbacli.2017.01.001

Lydeard, J. R., Lipkin-Moore, Z., Sheu, Y.-J., Stillman, B., Burgers, P. M., & Haber, J. E. (2010). Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. *Genes & Development*, *24*(11), 1133–1144. https://doi.org/10.1101/gad.1922610

Lyu, X., Chastain, M., & Chai, W. (2019). Genome-wide mapping and profiling of γH2AX binding hotspots in response to different replication stress inducers. *BMC Genomics*, *20*(1), 579. https://doi.org/10.1186/s12864-019-5934-4

MacDougall, C. A., Byun, T. S., Van, C., Yee, M., & Cimprich, K. A. (2007). The structural determinants of checkpoint activation. *Genes & Development*, *21*(8), 898–903. https://doi.org/10.1101/gad.1522607
Macheret, M., & Halazonetis, T. D. (2015). DNA replication stress as a hallmark of cancer. *Annual Review of Pathology: Mechanisms of Disease, 10*, 425–448. https://doi.org/10.1146/annurev-pathol-012414-040424

Madak, J. T., Bankhead, A., Cuthbertson, C. R., Showalter, H. D., & Neamati, N. (2019). Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer. *Pharmacology & Therapeutics, 195*, 111–131. https://doi.org/10.1016/j.pharmthera.2018.10.012

Magdalou, I., Lopez, B. S., Pasero, P., & Lambert, S. A. E. (2014). The causes of replication stress and their consequences on genome stability and cell fate. In *Seminars in Cell and Developmental Biology* (Vol. 30, pp. 154–164). Elsevier Ltd. https://doi.org/10.1016/j.semcdb.2014.04.035

Makridakis, N. M., & Reichardt, J. K. V. (2012). Translesion DNA Polymerases and Cancer. *Frontiers in Genetics, 3*. https://doi.org/10.3389/fgene.2012.00174

Malik, K., & Brown, K. W. (2000). Epigenetic gene deregulation in cancer. In *British Journal of Cancer* (Vol. 83, Issue 12, pp. 1583–1588). https://doi.org/10.1054/bjoc.2000.1549

Malkova, A., & Ira, G. (2013). Break-induced replication: functions and molecular mechanism. *Current Opinion in Genetics & Development, 23*(3), 271–279. https://doi.org/10.1016/j.gde.2013.05.007

Malumbres, M. (2014). Cyclin-dependent kinases. *Genome Biology, 15*(6), 122. https://doi.org/10.1186/gb4184

Malumbres, M., & Barbacid, M. (2005). Mammalian cyclin-dependent kinases. *Trends in Biochemical Sciences, 30*(11), 630–641. https://doi.org/10.1016/j.tibs.2005.09.005

Malumbres, M., & Barbacid, M. (2009). Cell cycle, CDKs and cancer: a changing paradigm. *Nature Reviews Cancer, 9*(3), 153–166. https://doi.org/10.1038/nrc2602

Manegold, C., Zatloukal, P., Krejcy, K., & Blatter, J. (2000). Gemcitabine in Non-Small Cell Lung Cancer (NSCLC). *Investigational New Drugs, 18*(1), 29–42. https://doi.org/10.1023/A:1006327729228

Maréchal, A., Li, J.-M., Ji, X. Y., Wu, C.-S., Yazinski, S. A., Nguyen, H. D., Liu, S., Jiménez, A. E., Jin, J., & Zou, L. (2014). PRP19 Transforms into a Sensor of RPA-ssDNA after DNA Damage and Drives ATR Activation via a Ubiquitin-Mediated Circuitry. *Molecular Cell, 53*(2), 235–246. https://doi.org/10.1016/j.molcel.2013.11.002

Marrero, V. A., & Symington, L. S. (2010). Extensive DNA End Processing by Exo1 and Sgs1 Inhibits Break-Induced Replication. *PLoS Genetics, 6*(7), e1001007. https://doi.org/10.1371/journal.pgen.1001007

Masai, H., & Arai, K.-I. (2002). Cdc7 kinase complex: A key regulator in the initiation of DNA replication. *Journal of Cellular Physiology, 190*(3), 287–296. https://doi.org/10.1002/jcp.10070

Mason, J. M., Chan, Y.-L., Weichselbaum, R. W., & Bishop, D. K. (2019). Non-enzymatic roles of human RAD51 at stalled replication forks. *Nature Communications, 10*(1), 4410. https://doi.org/10.1038/s41467-019-12297-0

Mathews, C. K. (2006). DNA precursor metabolism and genomic stability. *The FASEB Journal, 20*(9), 1300–1314. https://doi.org/10.1096/fj.06-5730rev

Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., & Elledge, S. J. (2000). Ataxia telangiectasia-mutated phosphorylates Chk2 *in vivo* and *in vitro*. *Proceedings of the National Academy of Sciences, 97*(19), 10389–10394. https://doi.org/10.1073/pnas.190030497
Mayle, R., Campbell, I. M., Beck, C. R., Yu, Y., Wilson, M., Shaw, C. A., Bjergbaek, L., Lupski, J. R., & Ira, G. (2015). Mus81 and converging forks limit the mutagenicity of replication fork breakage. *Science*, **349**(6249), 742–747. https://doi.org/10.1126/science.aaa8391

Mazouzi, A., Stukalov, A., Müller, A. C., Chen, D., Wiedner, M., Prochazkova, J., Chiang, S.-C., Schuster, M., Breitwieser, F. P., Pichlmair, A., El-Khamisy, S. F., Bock, C., Kralovics, R., Colinge, J., Bennett, K. L., & Loizou, J. I. (2016). A Comprehensive Analysis of the Dynamic Response to Aphidicolin-Mediated Replication Stress Uncovers Targets for ATM and ATMIN. *Cell Reports*, **15**(4), 893–908.
https://doi.org/10.1016/j celrep.2016.03.077

Mazouzi, A., Velimezi, G., & Loizou, J. I. (2014). DNA replication stress: Causes, resolution and disease. In *Experimental Cell Research* (Vol. 329, Issue 1, pp. 85–93). Academic Press Inc.
https://doi.org/10.1016/j.yexcr.2014.09.030

McCulloch, S. D., & Kunkel, T. A. (2008). The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. *Cell Research*, **18**(1), 148–161. https://doi.org/10.1038/cr.2008.4

McVey, M., Khodaverdian, V. Y., Meyer, D., Cerqueira, P. G., & Heyer, W.-D. (2016). Eukaryotic DNA Polymerases in Homologous Recombination. *Annual Review of Genetics*, **50**(1), 393–421.
https://doi.org/10.1146/annurev-genet-120215-035243

Méchali, M. (2010). Eukaryotic DNA replication origins: many choices for appropriate answers. *Nature Reviews Molecular Cell Biology*, **11**(10), 728–738. https://doi.org/10.1038/nrm2976

*Mechanism of Action of Classical Platinum Agents*. (n.d.).

Mei, Q., Huang, J., Chen, W., Tang, J., Xu, C., Yu, Q., Cheng, Y., Ma, L., Yu, X., & Li, S. (2017). Regulation of DNA replication-coupled histone gene expression. *Oncotarget*, **8**(55), 95005–95022.
https://doi.org/10.18632/oncotarget.21887

Meirelles, G. V., Perez, A. M., de Souza, E. E., Basei, F. L., Papa, P. F., Melo Hanchuk, T. D., Cardoso, V. B., & Kobarg, J. (2014). “Stop Ne(c)king around”: How interactomics contributes to functionally characterize Nek family kinases. *World Journal of Biological Chemistry*, **5**(2), 141–160.
https://doi.org/10.4331/wjbc.v5.i2.141

Mejlvang, J., Feng, Y., Alabert, C., Neelsen, K. J., Jasencakova, Z., Zhao, X., Lees, M., Sandelin, A., Pasero, P., Lopes, M., & Groth, A. (2014). New histone supply regulates replication fork speed and PCNA unloading. *Journal of Cell Biology*, **204**(1), 29–43. https://doi.org/10.1083/jcb.201305017

Mitrovski, B., Pressacco, J., Mandelbaum, S., & Erlichman, C. (1994). Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. *Cancer Chemotherapy and Pharmacology*, **35**(2), 109–114. https://doi.org/10.1007/BF00686631

Miyabe, I., Mizuno, K., Keszthelyi, A., Daigaku, Y., Skouteri, M., Mohebi, S., Kunkel, T. A., Murray, J. M., & Carr, A. M. (2015). Polymerase δ replicates both strands after homologous recombination–dependent fork restart. *Nature Structural & Molecular Biology*, **22**(11), 932–938.
https://doi.org/10.1038/nsmb.3100

Mizuno, K., Lambert, S., Baldacci, G., Murray, J. M., & Carr, A. M. (2009). Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism. *Genes & Development*, **23**(24), 2876–2886. https://doi.org/10.1101/gad.1863009
Moiseeva, T., Hood, B., Schamus, S., O'Connor, M. J., Conrads, T. P., & Bakkenist, C. J. (2017). ATR kinase inhibition induces unscheduled origin firing through a Cdc7-dependent association between GINS and And-1. *Nature Communications, 8*(1), 1392. https://doi.org/10.1038/s41467-017-01401-x

Mordes, D. A., Glick, G. G., Zhao, R., & Cortez, D. (2008). TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. *Genes & Development, 22*(11), 1478-1489. https://doi.org/10.1101/gad.1666208

Moriel-Carretero, M., & Aguilera, A. (2010). A Postincision-Deficient TFIIH Causes Replication Fork Breakage and Uncovers Alternative Rad51- or Pol32-Mediated Restart Mechanisms. *Molecular Cell*, 37(5), 690-701. https://doi.org/10.1016/j.molcel.2010.02.008

Moss, J., Tinline-Purvis, H., Walker, C. A., Folkes, L. K., Stratford, M. R., Hayles, J., Hoe, K.-L., Kim, D.-U., Park, H.-O., Kearsey, S. E., Fleck, O., Holmberg, C., Nielsen, O., & Humphrey, T. C. (2010). Break-induced ATR and Ddb1-Cul4 Cdt2 ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast. *Genes & Development*, 24(23), 2705-2716.
https://doi.org/10.1101/gad.1970810

Mouridsen, H. T., Alfthan, C., Bastholt, L., Bergh, J., Dalmark, M., Eksborg, S., Hellsten, S., Kjaer, M., Peterson, C., Skovsgård, T., Sørensen, J. B., Tropé, C., & Aabo, K. (1990). Current Status of Epirubicin (Farmorubicin) in the Treatment of Solid Tumours. *Acta Oncologica*, 29(3), 257-285.
https://doi.org/10.3109/02841869009089998

Mourón, S., Rodriguez-Acebes, S., Martínez-Jiménez, M. I., García-Gómez, S., Chocrón, S., Blanco, L., & Méndez, J. (2013). Repriming of DNA synthesis at stalled replication forks by human PrimPol. *Nature Structural & Molecular Biology*, 20(12), 1383-1389. https://doi.org/10.1038/nsmb.2719

Murfuni, I., Basile, G., Subramanyam, S., Malacaria, E., Bignami, M., Spies, M., Franchitto, A., & Pichierri, P. (2013). Survival of the Replication Checkpoint Deficient Cells Requires MUS81-RAD52 Function. *PLoS Genetics*, 9(10), e1003910. https://doi.org/10.1371/journal.pgen.1003910

Naffouje, R., Grover, P., Yu, H., Sendilnathan, A., Wolfe, K., Majd, N., Smith, E. P., Takeuchi, K., Senda, T., Kofuji, S., & Sasaki, A. T. (2019). Anti-tumor potential of IMP dehydrogenase inhibitors: A century-long story. In *Cancers* (Vol. 11, Issue 9). MDPI AG. https://doi.org/10.3390/cancers11091346

Nakahira, S., Nakamori, S., Tsujie, M., Takahashi, Y., Okami, J., Yoshioka, S., Yamasaki, M., Marubashi, S., Takemasa, I., Miyamoto, A., Takeda, Y., Nagano, H., Dono, K., Umeshita, K., Sakon, M., & Monden, M. (2007). Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. *International Journal of Cancer*, 120(6), 1355-1363.
https://doi.org/10.1002/ijc.22390

Nakanishi, M., Katsuno, Y., Niida, H., Murakami, H., & Shimada, M. (2010). Chk1-cyclin A/Cdk1 axis regulates origin firing programs in mammals. *Chromosome Research*, 18(1), 103-113.
https://doi.org/10.1007/s10577-009-9086-2

Nam, E. A., Zhao, R., Glick, G. G., Bansbach, C. E., Friedman, D. B., & Cortez, D. (2011). Thr-1989 Phosphorylation Is a Marker of Active Ataxia Telangiectasia-mutated and Rad3-related (ATR) Kinase. *Journal of Biological Chemistry*, 286(33), 28707-28714. https://doi.org/10.1074/jbc.M111.248914

Neelsen, K. J., & Lopes, M. (2015). Replication fork reversal in eukaryotes: From dead end to dynamic response. In *Nature Reviews Molecular Cell Biology* (Vol. 16, Issue 4, pp. 207-220). Nature Publishing Group. https://doi.org/10.1038/nrm3935
Neelsen, K. J., Zanini, I. M. Y., Mijic, S., Herrador, R., Zellweger, R., Ray Chaudhuri, A., Creavin, K. D., Blow, J. J., & Lopes, M. (2013). Deregulated origin licensing leads to chromosomal breaks by rereplication of a gapped DNA template. *Genes & Development*, 27(23), 2537–2542.
https://doi.org/10.1101/gad.226373.113

Nelson, D. M., Ye, X., Hall, C., Santos, H., Ma, T., Kao, G. D., Yen, T. J., Harper, J. W., & Adams, P. D. (2002). Coupling of DNA Synthesis and Histone Synthesis in S Phase Independent of Cyclin/cdk2 Activity. *Molecular and Cellular Biology*, 22(21), 7459–7472. https://doi.org/10.1128/MCB.22.21.7459-7472.2002

Niedzwiedz, W. (2016). Activating ATR, the devil's in the dETAA1l. *Nature Cell Biology*, 18(11), 1120–1122.
https://doi.org/10.1038/ncb3431

Nigović, B., Kujundžić, N., & Sanković, K. (2005). Electron transfer in N-hydroxyurea complexes with iron(III). *European Journal of Medicinal Chemistry*, 40(1), 51–55.
https://doi.org/10.1016/j.ejmech.2004.09.012

Niida, H., Katsuno, Y., Banerjee, B., Hande, M. P., & Nakanishi, M. (2007). Specific Role of Chk1 Phosphorylations in Cell Survival and Checkpoint Activation. *Molecular and Cellular Biology*, 27(7), 2572–2581. https://doi.org/10.1128/MCB.01611-06

Niida, H., Katsuno, Y., Sengoku, M., Shimada, M., Yukawa, M., Ikura, M., Ikura, T., Kohno, K., Shima, H., Suzuki, H., Tashiro, S., & Nakanishi, M. (2010). Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. *Genes & Development*, 24(4), 333–338. https://doi.org/10.1101/gad.1863810

Nilsson, I., & Hoffmann, I. (2000). Cell cycle regulation by the Cdc25 phosphatase family. In *Progress in Cell Cycle Research* (pp. 107–114). Springer US. https://doi.org/10.1007/978-1-4615-4253-7_10

Nimonkar, A. V., Genschel, J., Kinoshita, E., Polaczek, P., Campbell, J. L., Wyman, C., Modrich, P., & Kowalczykowski, S. C. (2011). BLM–DNA2–RPA–MRN and EXO1–BLM–RPA–MRN constitute two DNA end resection machineries for human DNA break repair. *Genes & Development*, 25(4), 350–362.
https://doi.org/10.1101/gad.2003811

Nishitani, H., & Lygerou, Z. (2002). Control of DNA replication licensing in a cell cycle. *Genes to Cells*, 7(6), 523–534. https://doi.org/10.1046/j.1365-2443.2002.00544.x

Noordermeer, S. M., Adam, S., Setiaputra, D., Barazas, M., Pettitt, S. J., Ling, A. K., Olivieri, M., Álvarez-Quilón, A., Moatti, N., Zimmermann, M., Annunziato, S., Krastev, D. B., Song, F., Brandsma, I., Frankum, J., Brough, R., Sherker, A., Landry, S., Szilard, R. K., ... Durocher, D. (2018). The shieldin complex mediates 53BP1-dependent DNA repair. *Nature*, 560(7716), 117–121.
https://doi.org/10.1038/s41586-018-0340-7

Nordlund, P., & Reichard, P. (2006). Ribonucleotide Reductases. *Annual Review of Biochemistry*, 75(1), 681–706. https://doi.org/10.1146/annurev.biochem.75.103004.142443

Nuno M. F. S. A. Cerqueira, & Ramos, M. J. (2007). Ribonucleotide Reductase: A Critical Enzyme for Cancer Chemotherapy and Antiviral Agents. *Recent Patents on Anti-Cancer Drug Discovery*, 2(1), 11–29.
https://doi.org/10.2174/157489207779561408

Ohtaka, K., Kohya, N., Sato, K., Kitajima, Y., Ide, T., Mitsuno, M., & Miyazaki, K. (2008). Ribonucleotide reductase subunit M1 is a possible chemoresistance marker to gemcitabine in biliary tract carcinoma. *Oncology Reports*, 20(2), 279–286.
Okesli, A., Khosla, C., & Bassik, M. C. (2017). Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy. *In Current Opinion in Biotechnology* (Vol. 48, pp. 127–134). Elsevier Ltd.
https://doi.org/10.1016/j.copbio.2017.03.010

Okita, N., Minato, S., Ohmi, E., Tanuma, S., & Higami, Y. (2012). DNA damage-induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism. *FEBS Letters, 586*(22), 3974–3979.
https://doi.org/10.1016/j.febslet.2012.09.048

Ono, H., Basson, M. D., & Ito, H. (2016). P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer. *Oncotarget*, 7(32), 51301–51310. https://doi.org/10.18632/oncotarget.10117

Orhan, E., Velazquez, C., Tabet, I., Sardet, C., & Theillet, C. (2021). Regulation of rad51 at the transcriptional and functional levels: What prospects for cancer therapy? *In Cancers* (Vol. 13, Issue 12). MDPI AG. https://doi.org/10.3390/cancers13122930

Ozeri-Galai, E., Lebofsky, R., Rahat, A., Bester, A. C., Bensimon, A., & Kerem, B. (2011). Failure of Origin Activation in Response to Fork Stalling Leads to Chromosomal Instability at Fragile Sites. *Molecular Cell, 43*(1), 122–131. https://doi.org/10.1016/j.molcel.2011.05.019

Ozeri-Galai, E., Schwartz, M., Rahat, A., & Kerem, B. (2008). Interplay between ATM and ATR in the regulation of common fragile site stability. *Oncogene*, 27(15), 2109–2117.
https://doi.org/10.1038/sj.onc.1210849

Paduch, R. (2015). Theories of cancer origin. *European Journal of Cancer Prevention*, 24(1), 57–67.
https://doi.org/10.1097/CEJ.0000000000000024

Pai, C. C., & Kearsey, S. E. (2017). A critical balance: DNTPs and the maintenance of genome stability. In *Genes* (Vol. 8, Issue 2). MDPI AG. https://doi.org/10.3390/genes8020057

Papavramidou, N., Papavramidis, T., & Demetriou, T. (2010). Ancient greek and greco-Roman methods in modern surgical treatment of cancer. *In Annals of Surgical Oncology* (Vol. 17, Issue 3, pp. 665–667).
https://doi.org/10.1245/s10434-009-0886-6

Pardo, B., & Aguilera, A. (2012). Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases. *PLoS Genetics*, 8(9), e1002979.
https://doi.org/10.1371/journal.pgen.1002979

Parker, W. B. (2009). Enzymology of Purine and Pyrimidine Antimetabolites Used in the Treatment of Cancer. *Chemical Reviews*, 109(7), 2880–2893. https://doi.org/10.1021/cr900028p

Parker, W. B., Shaddix, S. C., Chang, C. H., White, E. L., Rose, L. M., Brockman, R. W., Shortnacy, A. T., Montgomery, J. A., Secrist, J. A., & Bennett, L. L. (1991). Effects of 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine on K562 cellular metabolism and the inhibition of human ribonucleotide reductase and DNA polymerases by its 5'-triphosphate. *Cancer Research*, 51(9), 2386–2394.

Pasero, P., & Schwob, E. (2000). Think global, act local — how to regulate S phase from individual replication origins. *Current Opinion in Genetics & Development*, 10(2), 178–186.
https://doi.org/10.1016/S0959-437X(00)00067-8

Pasero, P., & Vindigni, A. (2017a). *Nucleases Acting at Stalled Forks: How to Reboot the Replication Program with a Few Shortcuts*. https://doi.org/10.1146/annurev-genet-120116
Patil, M., Pabla, N., & Dong, Z. (2013). Checkpoint kinase 1 in DNA damage response and cell cycle regulation. *Cellular and Molecular Life Sciences*, 70(21), 4009–4021. https://doi.org/10.1007/s00018-013-1307-3

Paulsen, R. D., Soni, D. V., Wollman, R., Hahn, A. T., Yee, M.-C., Guan, A., Hesley, J. A., Miller, S. C., Cromwell, E. F., Solow-Cordero, D. E., Meyer, T., & Cimprich, K. A. (2009). A Genome-wide siRNA Screen Reveals Diverse Cellular Processes and Pathways that Mediate Genome Stability. *Molecular Cell*, 35(2), 228–239. https://doi.org/10.1016/j.molcel.2009.06.021

Pavlova, N. N., & Thompson, C. B. (2016). The Emerging Hallmarks of Cancer Metabolism. *Cell Metabolism*, 23(1), 27–47. https://doi.org/10.1016/j.cmet.2015.12.006

Pepe, A., & West, S. C. (2014). MUS81-EME2 Promotes Replication Fork Restart. *Cell Reports*, 7(4), 1048–1055. https://doi.org/10.1016/j.celrep.2014.04.007

Perkhofer, L., Gout, J., Roger, E., Kude De Almeida, F., Baptista Simões, C., Wiesmüller, L., Seufferlein, T., & Kleger, A. (2021). DNA damage repair as a target in pancreatic cancer: State-of-the-art and future perspectives. In *Gut* (Vol. 70, Issue 3, pp. 606–617). BMJ Publishing Group. https://doi.org/10.1136/gutjnl-2019-319984

Petermann, E., Orta, M. L., Issaeva, N., Schultz, N., & Helleday, T. (2010). Hydroxyurea-Stalled Replication Forks Become Progressively Inactivated and Require Two Different RAD51-Mediated Pathways for Restart and Repair. *Molecular Cell*, 37(4), 492–502. https://doi.org/10.1016/j.molcel.2010.01.021

Peters, J.-M. (1998). SCF and APC: the Yin and Yang of cell cycle regulated proteolysis. *Current Opinion in Cell Biology*, 10(6), 759–768. https://doi.org/10.1016/S0955-0674(98)80119-1

Plunkett, W., Huang, P., & Gandhi, V. (1995). Preclinical characteristics of gemcitabine. *Anti-Cancer Drugs*, 6(Supplement 6), 7–13. https://doi.org/10.1097/00001813-199512006-00002

Plunkett, W., Huang, P., Searcy, C. E., & Gandhi, V. (1996). Gemcitabine: preclinical pharmacology and mechanisms of action. *Seminars in Oncology*, 23(5 Suppl 10), 3–15.

Podhorecka, M., Skladanowski, A., & Bozko, P. (2010). H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. *Journal of Nucleic Acids*, 2010, 1–9. https://doi.org/10.4061/2010/920161

Poggi, L., & Richard, G.-F. (2021). Alternative DNA Structures *In Vivo*: Molecular Evidence and Remaining Questions. *Microbiology and Molecular Biology Reviews*, 85(1). https://doi.org/10.1128/MMBR.00110-20

Poli, J., Tsaponina, O., Crabbé, L., Keszthelyi, A., Pantesco, V., Chabes, A., Lengronne, A., & Pasero, P. (2012). dNTP pools determine fork progression and origin usage under replication stress. *The EMBO Journal*, 31(4), 883–894. https://doi.org/10.1038/emboj.2011.470

Pommier, Y. (2013). Drugging Topoisomerases: Lessons and Challenges. *ACS Chemical Biology*, 8(1), 82–95. https://doi.org/10.1021/cb300648v

Pommier, Y., Leo, E., Zhang, H., & Marchand, C. (2010). DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial Drugs. *Chemistry & Biology*, 17(5), 421–433. https://doi.org/10.1016/j.chembiol.2010.04.012

Pon, J. R., & Marra, M. A. (2015). Driver and passenger mutations in cancer. *Annual Review of Pathology: Mechanisms of Disease*, 10, 25–50. https://doi.org/10.1146/annurev-pathol-012414-040312
Pontarin, G., Ferraro, P., Rampazzo, C., Kollberg, G., Holme, E., Reichard, P., & Bianchi, V. (2011). Deoxyribonucleotide Metabolism in Cycling and Resting Human Fibroblasts with a Missense Mutation in p53R2, a Subunit of Ribonucleotide Reductase. *Journal of Biological Chemistry, 286*(13), 11132-11140. https://doi.org/10.1074/jbc.M110.202283

Pontarin, G., Fijolek, A., Pizzo, P., Ferraro, P., Rampazzo, C., Pozzan, T., Thelander, L., Reichard, P. A., & Bianchi, V. (2008). Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage. *Proceedings of the National Academy of Sciences, 105*(46), 17801-17806. https://doi.org/10.1073/pnas.0808198105

Prakash, A., & Borgstahl, G. E. O. (2012). *The Structure and Function of Replication Protein A in DNA Replication* (pp. 171-196). https://doi.org/10.1007/978-94-007-4572-8_10

Puig, S., de Llanos, R., & Sanvisens, N. (2013). Function and Regulation of Yeast Ribonucleotide Reductase: Cell Cycle, Genotoxic Stress, and Iron Bioavailability. *Biomedical Journal, 36*(2), 51. https://doi.org/10.4103/2319-4170.110398

Qian, X., Li, X., Tan, L., Lee, J. H., Xia, Y., Cai, Q., Zheng, Y., Wang, H., Lorenzi, P. L., & Lu, Z. (2018). Conversion of prps hexamer to monomer by AMPK-mediated phosphorylation inhibits nucleotide synthesis in response to energy stress. *Cancer Discovery, 8*(1), 94-107. https://doi.org/10.1158/2159-8290.CD-17-0712

Quinet, A., Lemaçon, D., & Vindigni, A. (2017a). Replication Fork Reversal: Players and Guardians. In *Molecular Cell* (Vol. 68, Issue 5, pp. 830-833). Cell Press. https://doi.org/10.1016/j.molcel.2017.11.022

Rabinowitz, J. D., Hsiao, J. J., Gryncel, K. R., Kantrowitz, E. R., Feng, X.-J., Li, G., & Rabitz, H. (2008). Dissecting Enzyme Regulation by Multiple Allosteric Effectors: Nucleotide Regulation of Aspartate Transcarbamoylase. *Biochemistry, 47*(21), 5881-5888. https://doi.org/10.1021/bi8000566

Ragland, R. L., Patel, S., Rivard, R. S., Smith, K., Peters, A. A., Bielinsky, A.-K., & Brown, E. J. (2013). RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells. *Genes & Development, 27*(20), 2259-2273. https://doi.org/10.1101/gad.223180.113

Raimundo, L., Ramos, H., Loureiro, J. B., Calheiros, J., & Saraiva, L. (2020). BRCA1/P53: Two strengths in cancer chemoprevention. *Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1873*(1), 188339. https://doi.org/10.1016/j.bbcan.2020.188339

Rankin, P. W., Jacobson, E. L., Benjamin, R. C., Moss, J., & Jacobson, M. K. (1989). Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo. *The Journal of Biological Chemistry, 264*(8), 4312-4317.

Rao, Q., Liu, M., Tian, Y., Wu, Z., Hao, Y., Song, L., Qin, Z., Ding, C., Wang, H.-W., Wang, J., & Xu, Y. (2018). Cryo-EM structure of human ATR-ATRIP complex. *Cell Research, 28*(2), 143-156. https://doi.org/10.1038/cr.2017.158

Rassool, F. V., & Tomkinson, A. E. (2010). Targeting abnormal DNA double strand break repair in cancer. *Cellular and Molecular Life Sciences, 67*(21), 3699-3710. https://doi.org/10.1007/s00018-010-0493-5

Ray Chaudhuri, A., Hashimoto, Y., Herrador, R., Neelsen, K. J., Fachinetti, D., Bermejo, R., Cocito, A., Costanzo, V., & Lopes, M. (2012). Topoisomerase I poisoning results in PARP-mediated replication fork reversal. *Nature Structural & Molecular Biology, 19*(4), 417-423. https://doi.org/10.1038/nsmb.2258
Regairaz, M., Zhang, Y.-W., Fu, H., Agama, K. K., Tata, N., Agrawal, S., Aladjem, M. I., & Pommier, Y. (2011). Mus81-mediated DNA cleavage resolves replication forks stalled by topoisomerase I-DNA complexes. *Journal of Cell Biology, 195*(5), 739-749. https://doi.org/10.1083/jcb.201104003

Remus, D., Beuron, F., Tolun, G., Griffith, J. D., Morris, E. P., & Diffley, J. F. X. (2009). Concerted Loading of Mcm2-7 Double Hexamers around DNA during DNA Replication Origin Licensing. *Cell, 139*(4), 719-730. https://doi.org/10.1016/j.cell.2009.10.015

Remus, D., & Diffley, J. F. (2009). Eukaryotic DNA replication control: Lock and load, then fire. *Current Opinion in Cell Biology, 21*(6), 771-777. https://doi.org/10.1016/j.ceb.2009.08.002

Reynolds, C., Obasaju, C., Schell, M. J., Li, X., Zheng, Z., Boulware, D., Caton, J. R., DeMarco, L. C., O'Rourke, M. A., Shaw Wright, G., Boehm, K. A., Asmar, L., Bromund, J., Peng, G., Monberg, M. J., & Bepler, G. (2009). Randomized Phase III Trial of Gemcitabine-Based Chemotherapy With In Situ RRM1 and ERCC1 Protein Levels for Response Prediction in Non-Small-Cell Lung Cancer. *Journal of Clinical Oncology, 27*(34), 5808-5815. https://doi.org/10.1200/JCO.2009.21.9766

Rhind, N., & Gilbert, D. M. (2013). DNA Replication Timing. *Cold Spring Harbor Perspectives in Biology, 5*(8), a010132-a010132. https://doi.org/10.1101/cshperspect.a010132

Rice, A. M., & McLysaght, A. (2017). Dosage-sensitive genes in evolution and disease. *BMC Biology, 15*(1), 78. https://doi.org/10.1186/s12915-017-0418-y

Riess, C., Irmscher, N., Salewski, I., Strüder, D., Classen, C.-F., Große-Thie, C., Junghanss, C., & Maletzki, C. (2021). Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma—backbone or add-on in immune-oncology? *Cancer and Metastasis Reviews, 40*(1), 153-171. https://doi.org/10.1007/s10555-020-09940-4

Rodriguez, J., Boni, V., Hernández, A., Bitarte, N., Zarate, R., Ponz-Sarvisé, M., Chopitea, A., Bandres, E., & Garcia-Foncillas, J. (2011a). Association of RRM1-37A&gt;C polymorphism with clinical outcome in colorectal cancer patients treated with gemcitabine-based chemotherapy. *European Journal of Cancer, 47*(6), 839-847. https://doi.org/10.1016/j.ejca.2010.11.032

Rose, M. G., Farrell, M. P., & Schmitz, J. C. (2002). Thymidylate Synthase: A Critical Target for Cancer Chemotherapy. *Clinical Colorectal Cancer, 1*(4), 220-229. https://doi.org/10.3816/CCC.2002.n.003

Roussel, M. F. (1999). The INK4 family of cell cycle inhibitors in cancer. *Oncogene, 18*(38), 5311-5317. https://doi.org/10.1038/sj.onc.1202998

Rundle, S., Bradbury, A., Drew, Y., & Curtin, N. (2017). Targeting the ATR-CHK1 Axis in Cancer Therapy. *Cancers, 9*(12), 41. https://doi.org/10.3390/cancers9050041

RUTMAN, R. J., CANTAROW, A., & PASCHKIS, K. E. (1954). Studies in 2-acetylaminofluorene carcinogenesis. III. The utilization of uracil-2-C14 by preneoplastic rat liver and rat hepatoma. *Cancer Research, 14*(2), 119-123.

Sadoni, N., Langer, S., Fauth, C., Bernardi, G., Cremer, T., Turner, B. M., & Zink, D. (1999). Nuclear Organization of Mammalian Genomes. *Journal of Cell Biology, 146*(6), 1211-1226. https://doi.org/10.1083/jcb.146.6.1211

Saini, N., Zhang, Y., Usdin, K., & Lobachev, K. S. (2013). When secondary comes first – The importance of non-canonical DNA structures. *Biochimie, 95*(2), 117-123. https://doi.org/10.1016/j.biochi.2012.10.005
Saini, P., Li, Y., & Dobbelstein, M. (2015). Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress. *Oncotarget*, *6*(15), 13072-13087. https://doi.org/10.18632/oncotarget.3865

Saldivar, J. C., Cortez, D., & Cimprich, K. A. (2017). The essential kinase ATR: Ensuring faithful duplication of a challenging genome. In *Nature Reviews Molecular Cell Biology* (Vol. 18, Issue 10, pp. 622–636). Nature Publishing Group. https://doi.org/10.1038/nrm.2017.67

Sale, J. E. (2013). Translesion DNA Synthesis and Mutagenesis in Eukaryotes. *Cold Spring Harbor Perspectives in Biology*, *5*(3), a012708–a012708. https://doi.org/10.1101/cshperspect.a012708

Saleh-Gohari, N., Bryant, H. E., Schultz, N., Parker, K. M., Cassel, T. N., & Helleday, T. (2005). Spontaneous Homologous Recombination Is Induced by Collapsed Replication Forks That Are Caused by Endogenous DNA Single-Strand Breaks. *Molecular and Cellular Biology*, *25*(16), 7158-7169.
https://doi.org/10.1128/MCB.25.16.7158-7169.2005

Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997). Conservation of the Chk1 Checkpoint Pathway in Mammals: Linkage of DNA Damage to Cdk Regulation Through Cdc25. *Science*, *277*(5331), 1497-1501.
https://doi.org/10.1126/science.277.5331.1497

Santi, D. V., McHenry, C. S., & Sommer, H. (1974). Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. *Biochemistry*, *13*(3), 471-481. https://doi.org/10.1021/bi00700a012

Santocanale, C., & Diffley, J. F. X. (1998). A Mec1- and Rad53-dependent checkpoint controls late-firing origins of DNA replication. *Nature*, *395*(6702), 615-618. https://doi.org/10.1038/27001

Sarker, A. H., Trego, K. S., Zhang, W., Jacob, P., Snijders, A. M., Mao, J. H., Schick, S. F., Cooper, P. K., & Hang, B. (2020). Thirdhand smoke exposure causes replication stress and impaired transcription in human lung cells. *Environmental and Molecular Mutagenesis*, *61*(6), 635-646.
https://doi.org/10.1002/em.22372

Sarkies, P., Reams, C., Simpson, L. J., & Sale, J. E. (2010). Epigenetic Instability due to Defective Replication of Structured DNA. *Molecular Cell*, *40*(5), 703-713. https://doi.org/10.1016/j.molcel.2010.11.009

Sartori, A. A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., & Jackson, S. P. (2007). Human CtIP promotes DNA end resection. *Nature*, *450*(7169), 509-514.
https://doi.org/10.1038/nature06337

Sasaki, T., Ramanathan, S., Okuno, Y., Kumagai, C., Shaikh, S. S., & Gilbert, D. M. (2006). The Chinese Hamster Dihydrofolate Reductase Replication Origin Decision Point Follows Activation of Transcription and Suppresses Initiation of Replication within Transcription Units. *Molecular and Cellular Biology*, *26*(3), 1051-1062. https://doi.org/10.1128/MCB.26.3.1051-1062.2006

Schlacher, K., Christ, N., Siaud, N., Egashira, A., Wu, H., & Jasin, M. (2011). Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. *Cell*, *145*(4), 529-542. https://doi.org/10.1016/j.cell.2011.03.041

Schlacher, K., Wu, H., & Jasin, M. (2012). A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1/2. *Cancer Cell*, *22*(1), 106-116.
https://doi.org/10.1016/j.ccr.2012.05.015

Schmitt, E., Boutros, R., Froment, C., Monsarrat, B., Ducommun, B., & Dozier, C. (2006). CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage. *Journal of Cell Science*, *119*(20), 4269-4275. https://doi.org/10.1242/jcs.03200
Schwartsmann, G., Dodion, P., Vermorken, J. B., ten Bokkel Huinink, W. W., Joggi, J., Winograd, B., Gall, H., Simonetti, G., van der Vijgh, W. J. F., van Hennik, M. B., Crespeigne, N., & Pinedo, H. M. (1990). Phase I study of Brequinar sodium (NSC 368390) in patients with solid malignancies. *Cancer Chemotherapy and Pharmacology*, 25(5), 345-351. https://doi.org/10.1007/BF00686235

Scully, R., Panday, A., Elango, R., & Willis, N. A. (2019). DNA double-strand break repair-pathway choice in somatic mammalian cells. *Nature Reviews Molecular Cell Biology*, 20(11), 698-714.
https://doi.org/10.1038/s41580-019-0152-0

Sedletska, Y., Fourrier, L., & Malinge, J.-M. (2007). Modulation of MutS ATP-dependent Functional Activities by DNA containing a Cisplatin Compound Lesion (Base Damage and Mismatch). *Journal of Molecular Biology*, 369(1), 27-40. https://doi.org/10.1016/j.jmb.2007.02.048

Seiler, J. A., Conti, C., Syed, A., Aladjem, M. I., & Pommier, Y. (2007). The Intra-S-Phase Checkpoint Affects both DNA Replication Initiation and Elongation: Single-Cell and -DNA Fiber Analyses. *Molecular and Cellular Biology*, 27(16), 5806-5818. https://doi.org/10.1128/MCB.02278-06

Sepkowitz, K. A. (2011). One Hundred Years of Salvarsan. *New England Journal of Medicine*, 365(4), 291-293. https://doi.org/10.1056/NEJMp1105345

Sessa, C., Zucchetti, M., Davoli, E., Califano, R., Cavalli, F., Frustaci, S., Gumbrell, L., Sulkes, A., Winograd, B., & D'Incalci, M. (1991). Phase I and Clinical Pharmacological Evaluation of Aphidicolin Glycinate. *JNCI Journal of the National Cancer Institute*, 83(16), 1160-1164.
https://doi.org/10.1093/jnci/83.16.1160

Setiaputra, D., & Durocher, D. (2019). Shieldin – the protector of <scp>DNA</scp> ends. *EMBO Reports*, 20(5). https://doi.org/10.15252/embr.201847560

Shelton, J., Lu, X., Hollenbaugh, J. A., Cho, J. H., Amblard, F., & Schinazi, R. F. (2016). Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs. *Chemical Reviews*, 116(23), 14379-14455. https://doi.org/10.1021/acs.chemrev.6b00209

Sheu, Y.-J., & Stillman, B. (2010). The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in Mcm4. *Nature*, 463(7277), 113-117. https://doi.org/10.1038/nature08647

Shibata, A., Moiani, D., Arvai, A. S., Perry, J., Harding, S. M., Genois, M.-M., Maity, R., van Rossum-Fikkert, S., Kertokalio, A., Romoli, F., Ismail, A., Ismalaj, E., Petricci, E., Neale, M. J., Bristow, R. G., Masson, J.-Y., Wyman, C., Jeggo, P. A., & Tainer, J. A. (2014). DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities. *Molecular Cell*, 53(1), 7-18.
https://doi.org/10.1016/j.molcel.2013.11.003

Shiotani, B., & Zou, L. (2009a). ATR signaling at a glance. *Journal of Cell Science*, 122(3), 301-304.
https://doi.org/10.1242/jcs.035105

Shrivastav, M., De Haro, L. P., & Nickoloff, J. A. (2008). Regulation of DNA double-strand break repair pathway choice. *Cell Research*, 18(1), 134-147. https://doi.org/10.1038/cr.2007.111

Sidorova, J. (2017). A game of substrates: replication fork remodeling and its roles in genome stability and chemo-resistance. *Cell Stress*, 1(3), 115-133. https://doi.org/10.15698/cst2017.12.114

Singletary, K. W., & Gapstur, S. M. (2001). Alcohol and Breast Cancer. *JAMA*, 286(17), 2143.
https://doi.org/10.1001/jama.286.17.2143
Sinha, R. P., & Häder, D.-P. (2002). UV-induced DNA damage and repair: a review. *Photochemical & Photobiological Sciences*, 1(4), 225-236. https://doi.org/10.1039/b201230h

Smith, C. E., Llorente, B., & Symington, L. S. (2007). Template switching during break-induced replication. *Nature*, 447(7140), 102–105. https://doi.org/10.1038/nature05723

Smith, D. I., Zhu, Y., McAvoy, S., & Kuhn, R. (2006). Common fragile sites, extremely large genes, neural development and cancer. *Cancer Letters*, 232(1), 48–57.
https://doi.org/10.1016/j.canlet.2005.06.049

Smith, L. H., & Baker, F. A. (1959). PYRIMIDINE METABOLISM IN MAN. I. THE BIOSYNTHESIS OF OROTIC ACID*†. *Journal of Clinical Investigation*, 38(5), 798-809. https://doi.org/10.1172/JCI103862

SMITH, L. H., BAKER, F. A., & SULLIVAN, M. (1960). Pyrimidine metabolism in man. II. Studies of leukemic cells. *Blood*, 15, 360-369.

Smith, L., Liu, S. J., Goodrich, L., Jacobson, D., Degnin, C., Bentley, N., Carr, A., Flaggs, G., Keegan, K., Hoekstra, M., & Thayer, M. J. (1998). Duplication of ATR inhibits MyoD, induces aneuploidy and eliminates radiation-induced G1 arrest. *Nature Genetics*, 19(1), 39-46.
https://doi.org/10.1038/ng0598-39

Sommer, H., & Santi, D. V. (1974). Purification and amino acid analysis of an active site peptide from thymidylate synthetase containing covalently bound 5-fluoro-2'-deoxyuridylate and methylenetetrahydrofolate. *Biochemical and Biophysical Research Communications*, 57(3), 689-695.
https://doi.org/10.1016/0006-291X(74)90601-9

Sørensen, C. S., Hansen, L. T., Dziegielewski, J., Syljuåsen, R. G., Lundin, C., Bartek, J., & Helleday, T. (2005). The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. *Nature Cell Biology*, 7(2), 195-201. https://doi.org/10.1038/ncb1212

Sørlie, T., Tibshirani, R., Parker, J., Hastie, T., Marron, J. S., Nobel, A., Deng, S., Johnsen, H., Pesich, R., Geisler, S., Demeter, J., Perou, C. M., Lønning, P. E., Brown, P. O., Børresen-Dale, A.-L., & Botstein, D. (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. *Proceedings of the National Academy of Sciences*, 100(14), 8418-8423.
https://doi.org/10.1073/pnas.0932692100

Sotiriou, S. K., Kamileri, I., Lugli, N., Evangelou, K., Da-Ré, C., Huber, F., Padayachy, L., Tardy, S., Nicati, N. L., Barriot, S., Ochs, F., Lukas, C., Lukas, J., Gorgoulis, V. G., Scapozza, L., & Halazonetis, T. D. (2016). Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. *Molecular Cell*, 64(6), 1127-1134. https://doi.org/10.1016/j.molcel.2016.10.038

Spiegel, J., Adhikari, S., & Balasubramanian, S. (2020). The Structure and Function of DNA G-Quadruplexes. *Trends in Chemistry*, 2(2), 123-136. https://doi.org/10.1016/j.trechm.2019.07.002

Srinivasan, S. V., Dominguez-Sola, D., Wang, L. C., Hyrien, O., & Gautier, J. (2013). Cdc45 Is a Critical Effector of Myc-Dependent DNA Replication Stress. *Cell Reports*, 3(5), 1629-1639.
https://doi.org/10.1016/j.celrep.2013.04.002

Stirling, P. C., Chan, Y. A., Minaker, S. W., Aristizabal, M. J., Barrett, I., Sipahimalani, P., Kobor, M. S., & Hieter, P. (2012). R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. *Genes & Development*, 26(2), 163-175. https://doi.org/10.1101/gad.179721.111

Stubbe, J., Van, W. A., & Donk, D. (n.d.). Ribonucleotide reductases: radical enzymes with suicidal tendencies.
Sule, R. O., Condon, L., & Gomes, A. V. (2022). A Common Feature of Pesticides: Oxidative Stress - The Role of Oxidative Stress in Pesticide-Induced Toxicity. In *Oxidative Medicine and Cellular Longevity* (Vol. 2022). Hindawi Limited. https://doi.org/10.1155/2022/5563759

Sun, D., & Hurley, L. H. (2010). *Biochemical Techniques for the Characterization of G-Quadruplex Structures: EMSA, DMS Footprinting, and DNA Polymerase Stop Assay* (pp. 65–79). https://doi.org/10.1007/978-1-59745-363-9_5

Sur, S., & Agrawal, D. K. (2016). Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. *Molecular and Cellular Biochemistry*, **416**(1–2), 33–46. https://doi.org/10.1007/s11010-016-2693-2

Sy, S. M. H., Huen, M. S. Y., & Chen, J. (2009). PALB2 is an integral component of the BRCA complex required for homologous recombination repair. *Proceedings of the National Academy of Sciences*, **106**(17), 7155–7160. https://doi.org/10.1073/pnas.0811159106

Sykes, D. B. (2018). The emergence of dihydroorotate dehydrogenase (DHODH) as a therapeutic target in acute myeloid leukemia. *Expert Opinion on Therapeutic Targets*, **22**(11), 893–898. https://doi.org/10.1080/14728222.2018.1536748

Takahashi, M. (1987). A model for the spatio-temporal organization of DNA replication in mammalian cells. *Journal of Theoretical Biology*, **129**(1), 91–115. https://doi.org/10.1016/S0022-5193(87)80205-9

Takai, H., Tominaga, K., Motoyama, N., Minamishima, Y. A., Nagahama, H., Tsukiyama, T., Ikeda, K., Nakayama, K., Nakanishi, M., & Nakayama, K. (2000). Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. *Genes & Development*, **14**(12), 1439–1447.

Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., & Nakamura, Y. (2000a). A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. *Nature*, **404**(6773), 42–49. https://doi.org/10.1038/35003506

Técher, H., Koundrioukoff, S., Carignon, S., Wilhelm, T., Millot, G. A., Lopez, B. S., Brison, O., & Debatisse, M. (2016). Signaling from Mus81-Eme2-Dependent DNA Damage Elicited by Chk1 Deficiency Modulates Replication Fork Speed and Origin Usage. *Cell Reports*, **14**(5), 1114–1127. https://doi.org/10.1016/j.celrep.2015.12.093

Thanasoula, M., Escandell, J. M., Suwaki, N., & Tarsounas, M. (2012). ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres. *The EMBO Journal*, **31**(16), 3398–3410. https://doi.org/10.1038/emboj.2012.191

Thangavel, S., Berti, M., Levikova, M., Pinto, C., Gomathinayagam, S., Vujanovic, M., Zellweger, R., Moore, H., Lee, E. H., Hendrickson, E. A., Cejka, P., Stewart, S., Lopes, M., & Vindigni, A. (2015). DNA2 drives processing and restart of reversed replication forks in human cells. *Journal of Cell Biology*, **208**(5), 545–562. https://doi.org/10.1083/jcb.201406100

Thorslund, T., McIlwraith, M. J., Compton, S. A., Lekomtsev, S., Petronczki, M., Griffith, J. D., & West, S. C. (2010). The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. *Nature Structural & Molecular Biology*, **17**(10), 1263–1265. https://doi.org/10.1038/nsmb.1905

Tibbetts, R. S., Cortez, D., Brumbaugh, K. M., Scully, R., Livingston, D., Elledge, S. J., & Abraham, R. T. (2000). Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. *Genes and Development*, **14**(23), 2989–3002. https://doi.org/10.1101/gad.851000
Toledo, L. I., Altmeyer, M., Rask, M. B., Lukas, C., Larsen, D. H., Povlsen, L. K., Bekker-Jensen, S., Mailand, N., Bartek, J., & Lukas, J. (2013). XATR prohibits replication catastrophe by preventing global exhaustion of RPA. *Cell*, **155**(5), 1088. https://doi.org/10.1016/j.cell.2013.10.043

Toledo, L., Neelsen, K. J., & Lukas, J. (2017). Replication Catastrophe: When a Checkpoint Fails because of Exhaustion. In *Molecular Cell* (Vol. 66, Issue 6, pp. 735–749). Cell Press. https://doi.org/10.1016/j.molcel.2017.05.001

Tomasetti, C., Li, L., & Vogelstein, B. (2017). Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. *Science*, **355**(6331), 1330–1334. https://doi.org/10.1126/science.aaf9011

Tong, X., Smith, J., Bukreyeva, N., Koma, T., Manning, J. T., Kalkeri, R., Kwong, A. D., & Paessler, S. (2018). Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens. *Antiviral Research*, **149**, 34–40. https://doi.org/10.1016/j.antiviral.2017.11.004

Trentham-Dietz, A., Newcomb, P. A., Egan, K. M., Titus-Ernsto€, L., Baron, J. A., Storer, B. E., Stampfer, M., & Willett, W. C. (n.d.). *Weight change and risk of postmenopausal breast cancer (United States)*.

Trenz, K., Smith, E., Smith, S., & Costanzo, V. (2006). ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. *The EMBO Journal*, **25**(8), 1764–1774. https://doi.org/10.1038/sj.emboj.7601045

Tsantoulis, P. K., Kotsinas, A., Sfikakis, P. P., Evangelou, K., Sideridou, M., Levy, B., Mo, L., Kittas, C., Wu, X.-R., Papavassiliou, A. G., & Gorgoulis, V. G. (2008). Oncogene-induced replication stress preferentially targets common fragile sites in preneoplastic lesions. A genome-wide study. *Oncogene*, **27**(23), 3256–3264. https://doi.org/10.1038/sj.onc.1210989

Tuduri, S., Crabbé, L., Conti, C., Tourrière, H., Holtgreve-Grez, H., Jauch, A., Pantesco, V., De Vos, J., Thomas, A., Theillet, C., Pommier, Y., Tazi, J., Coquelle, A., & Pasero, P. (2009). Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. *Nature Cell Biology*, **11**(11), 1315–1324. https://doi.org/10.1038/ncb1984

Turner, B. M. (2000). Histone acetylation and an epigenetic code. *BioEssays*, **22**(9), 836–845. https://doi.org/10.1002/1521-1878(200009)22:9<836::AID-BIES9>3.0.CO;2-X

Turner, B. M. (2002). Cellular Memory and the Histone Code. *Cell*, **111**(3), 285–291. https://doi.org/10.1016/S0092-8674(02)01080-2

Turner, N., Tutt, A., & Ashworth, A. (2004). Hallmarks of “BRCAness” in sporadic cancers. *Nature Reviews Cancer*, **4**(10), 814–819. https://doi.org/10.1038/nrc1457

Turner, N., Tutt, A., & Ashworth, A. (2005). Targeting the DNA repair defect of BRCA tumours. In *Current Opinion in Pharmacology* (Vol. 5, Issue 4 SPEC. ISS., pp. 388–393). Elsevier BV. https://doi.org/10.1016/j.coph.2005.03.006

Ubhi, T., & Brown, G. W. (2019a). Exploiting DNA replication stress for cancer treatment. In *Cancer Research* (Vol. 79, Issue 8, pp. 1730–1739). American Association for Cancer Research Inc. https://doi.org/10.1158/0008-5472.CAN-18-3631

Vaisman, A., & Woodgate, R. (2017). Translesion DNA polymerases in eukaryotes: what makes them tick? *Critical Reviews in Biochemistry and Molecular Biology*, **52**(3), 274–303. https://doi.org/10.1080/10409238.2017.1291576
Vallerga, M. B., Mansilla, S. F., Federico, M. B., Bertolin, A. P., & Gottifredi, V. (2015). Rad51 recombinase prevents Mre11 nuclease-dependent degradation and excessive PrimPol-mediated elongation of nascent DNA after UV irradiation. *Proceedings of the National Academy of Sciences*, 112(48). https://doi.org/10.1073/pnas.1508543112

Van, C., Yan, S., Michael, W. M., Waga, S., & Cimprich, K. A. (2010). Continued primer synthesis at stalled replication forks contributes to checkpoint activation. *Journal of Cell Biology*, 189(2), 233-246. https://doi.org/10.1083/jcb.200909105

Van Middendorp, J. J., Sanchez, G. M., & Burridge, A. L. (2010). The Edwin Smith papyrus: A clinical reappraisal of the oldest known document on spinal injuries. In *European Spine Journal* (Vol. 19, Issue 11, pp. 1815-1823). https://doi.org/10.1007/s00586-010-1523-6

Vassin, V. M., Anantha, R. W., Sokolova, E., Kanner, S., & Borowiec, J. A. (2009). Human RPA phosphorylation by ATR stimulates DNA synthesis and prevents ssDNA accumulation during DNA-replication stress. *Journal of Cell Science*, 122(22), 4070-4080. https://doi.org/10.1242/jcs.053702

Velázquez, Carolina et al. "BRCA1-methylated triple negative breast cancers previously exposed to neoadjuvant chemotherapy from RAD51 foci and respond poorly to olaparib." *Frontiers in Oncology* 13 (2023): n. pag.

Velie, E., Kulldorff, M., Schairer, C., Block, G., Albanes, D., & Schatzkin, A. (n.d.). *Dietary Fat, Fat Subtypes, and Breast Cancer in Postmenopausal Women: a Prospective Cohort Study*. https://academic.oup.com/jnci/article/92/10/833/2905771

Vesela, E., Chroma, K., Turi, Z., & Mistrik, M. (2017). Common chemical inductors of replication stress: Focus on cell-based studies. In *Biomolecules* (Vol. 7, Issue 1). MDPI AG. https://doi.org/10.3390/biom7010019

Villa, E., Ali, E. S., Sahu, U., & Ben-Sahra, I. (2019a). Cancer cells tune the signaling pathways to empower de novo synthesis of nucleotides. In *Cancers* (Vol. 11, Issue 5). MDPI AG. https://doi.org/10.3390/cancers11050688

Vincent, K., Pichler, M., Lee, G.-W., & Ling, H. (2014). MicroRNAs, Genomic Instability and Cancer. *International Journal of Molecular Sciences*, 15(8), 14475-14491. https://doi.org/10.3390/ijms150814475

Vodermaier, H. C. (2004). APC/C and SCF: Controlling Each Other and the Cell Cycle. *Current Biology*, 14(18), R787-R796. https://doi.org/10.1016/j.cub.2004.09.020

Vujanovic, M., Krietsch, J., Raso, M. C., Terraneo, N., Zellweger, R., Schmid, J. A., Taglialatela, A., Huang, J.-W., Holland, C. L., Zwicky, K., Herrador, R., Jacobs, H., Cortez, D., Ciccia, A., Penengo, L., & Lopes, M. (2017). Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity. *Molecular Cell*, 67(5), 882-890.e5. https://doi.org/10.1016/j.molcel.2017.08.010

Wahba, L., Amon, J. D., Koshland, D., & Vuica-Ross, M. (2011). RNase H and Multiple RNA Biogenesis Factors Cooperate to Prevent RNA:DNA Hybrids from Generating Genome Instability. *Molecular Cell*, 44(6), 978-988. https://doi.org/10.1016/j.molcel.2011.10.017

Walworth, N., Davey, S., & Beach, D. (1993). Fission yeast chkl protein kinase links the rad checkpoint pathway to cdc2. *Nature*, 363(6427), 368-371. https://doi.org/10.1038/363368a0
Wan, L., Lou, J., Xia, Y., Su, B., Liu, T., Cui, J., Sun, Y., Lou, H., & Huang, J. (2013). hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity. *EMBO Reports*, **14**(12), 1104–1112. https://doi.org/10.1038/embor.2013.159

Wang, C., Zhang, B., Krüger, A., Du, X., Visser, L., Dömling, A. S. S., Wrenger, C., & Groves, M. R. (2022). Discovery of Small-Molecule Allosteric Inhibitors of PfATC as Antimalarials. *Journal of the American Chemical Society*, **144**(41), 19070–19077. https://doi.org/10.1021/jacs.2c08128

Wang, J. C. (2002). Cellular roles of DNA topoisomerases: a molecular perspective. *Nature Reviews Molecular Cell Biology*, **3**(6), 430–440. https://doi.org/10.1038/nrm831

Wang, J., Dong, H., Chionh, Y. H., McBee, M. E., Sirirungruang, S., Cunningham, R. P., Shi, P.-Y., & Dedon, P. C. (2016). The role of sequence context, nucleotide pool balance and stress in 2'-deoxynucleotide misincorporation in viral, bacterial and mammalian RNA. *Nucleic Acids Research*, **44**(18), 8962–8975. https://doi.org/10.1093/nar/gkw572

Wang, J., Han, X., Feng, X., Wang, Z., & Zhang, Y. (2012). Coupling Cellular Localization and Function of Checkpoint Kinase 1 (Chk1) in Checkpoints and Cell Viability. *Journal of Biological Chemistry*, **287**(30), 25501–25509. https://doi.org/10.1074/jbc.M112.350397

Wang, J., Lohman, G. J. S., & Stubbe, J. (2007). Enhanced subunit interactions with gemcitabine-5'-diphosphate inhibit ribonucleotide reductases. *Proceedings of the National Academy of Sciences*, **104**(36), 14324–14329. https://doi.org/10.1073/pnas.0706803104

Ward, I. M., & Chen, J. (2001). Histone H2AX Is Phosphorylated in an ATR-dependent Manner in Response to Replicative Stress. *Journal of Biological Chemistry*, **276**(51), 47759–47762. https://doi.org/10.1074/jbc.C100569200

Warren, N. J. H., & Eastman, A. (2020a). Comparison of the different mechanisms of cytotoxicity induced by checkpoint kinase I inhibitors when used as single agents or in combination with DNA damage. In *Oncogene* (Vol. 39, Issue 7, pp. 1389–1401). Springer Nature. https://doi.org/10.1038/s41388-019-1079-9

Wijerathna, S. R., Ahmad, Md. F., Xu, H., Fairman, J. W., Zhang, A., Kaushal, P. S., Wan, Q., Kiser, J., & Dealwis, C. G. (2011). Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer Chemotherapy. *Pharmaceuticals*, **4**(10), 1328–1354. https://doi.org/10.3390/ph4101328

Wilhelm, T., Magdalou, I., Barascu, A., Técher, H., Debatisse, M., & Lopez, B. S. (2014). Spontaneous slow replication fork progression elicits mitosis alterations in homologous recombination-deficient mammalian cells. *Proceedings of the National Academy of Sciences*, **111**(2), 763–768. https://doi.org/10.1073/pnas.1311520111

Williams, G. H., & Stoeber, K. (2012). The cell cycle and cancer. *The Journal of Pathology*, **226**(2), 352–364. https://doi.org/10.1002/path.3022

Williams, J. S., & Kunkel, T. A. (2014). Ribonucleotides in DNA: Origins, repair and consequences. *DNA Repair*, **19**, 27–37. https://doi.org/10.1016/j.dnarep.2014.03.029

Wilson, P. M., Danenberg, P. V., Johnston, P. G., Lenz, H. J., & Ladner, R. D. (2014). Standing the test of time: Targeting thymidylate biosynthesis in cancer therapy. In *Nature Reviews Clinical Oncology* (Vol. 11, Issue 5, pp. 282–298). Nature Publishing Group. https://doi.org/10.1038/nrclinonc.2014.51
Wu, H. liang, Gong, Y., Ji, P., Xie, Y. fan, Jiang, Y. Z., & Liu, G. yu. (2022). Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy. In *Journal of Hematology and Oncology* (Vol. 15, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13045-022-01263-x

Wu, Y., Lee, S.-H., Williamson, E. A., Reinert, B. L., Cho, J. H., Xia, F., Jaiswal, A. S., Srinivasan, G., Patel, B., Brantley, A., Zhou, D., Shao, L., Pathak, R., Hauer-Jensen, M., Singh, S., Kong, K., Wu, X., Kim, H.-S., Beissbarth, T., ... Hromas, R. A. (2015). EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair. *PLOS Genetics*, *11*(12), e1005675. https://doi.org/10.1371/journal.pgen.1005675

Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006). Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2. *Molecular Cell*, *22*(6), 719-729. https://doi.org/10.1016/j.molcel.2006.05.022

Xu, H., Faber, C., Uchiki, T., Racca, J., & Dealwis, C. (2006). Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly. *Proceedings of the National Academy of Sciences*, *103*(11), 4028-4033. https://doi.org/10.1073/pnas.0600440103

Xu, Y., & Her, C. (2015). Inhibition of Topoisomerase (DNA) I (TOP1): DNA Damage Repair and Anticancer Therapy. *Biomolecules*, *5*(3), 1652-1670. https://doi.org/10.3390/biom5031652

Yang, J. (2003). ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. *Carcinogenesis*, *24*(10), 1571-1580. https://doi.org/10.1093/carcin/bgg137

Yarden, R. I., Metsuyanim, S., Pickholtz, I., Shabbeer, S., Tellio, H., & Papa, M. Z. (2012). BRCA1-dependent Chk1 phosphorylation triggers partial chromatin disassociation of phosphorylated Chk1 and facilitates S-phase cell cycle arrest. *The International Journal of Biochemistry & Cell Biology*, *44*(11), 1761-1769. https://doi.org/10.1016/j.biocel.2012.06.026

Yarden, R. I., Pardo-Reoyo, S., Sgagias, M., Cowan, K. H., & Brody, L. C. (2002). BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. *Nature Genetics*, *30*(3), 285-289. https://doi.org/10.1038/ng837

Yeeles, J. T. P., Poli, J., Marians, K. J., & Pasero, P. (2013). Rescuing Stalled or Damaged Replication Forks. *Cold Spring Harbor Perspectives in Biology*, *5*(5), a012815-a012815. https://doi.org/10.1101/cshperspect.a012815

Yekezare, M., Gómez-González, B., & Diffley, J. F. X. (2013). Controlling DNA replication origins in response to DNA damage – inhibit globally, activate locally. *Journal of Cell Science*, *126*(6), 1297-1306. https://doi.org/10.1242/jcs.096701

Yeo, J. E., Lee, E. H., Hendrickson, E. A., & Sobeck, A. (2014). CtIP mediates replication fork recovery in a FANCD2-regulated manner. *Human Molecular Genetics*, *23*(14), 3695-3705. https://doi.org/10.1093/hmg/ddu078

Yoo, H. Y., Kumagai, A., Shevchenko, A., Shevchenko, A., & Dunphy, W. G. (2007). Ataxia-telangiectasia Mutated (ATM)-dependent Activation of ATR Occurs through Phosphorylation of TopBP1 by ATM. *Journal of Biological Chemistry*, *282*(24), 17501-17506. https://doi.org/10.1074/jbc.M701770200

Yoshioka, A., Tanaka, S., Hiraoka, O., Koyama, Y., Hirota, Y., Ayusawa, D., Seno, T., Garrett, C., & Wataya, Y. (1987). Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. *The Journal of Biological Chemistry*, *262*(17), 8235-8241.
Yu, X., Fu, S., Lai, M., Baer, R., & Chen, J. (2006). BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP. *Genes & Development*, 20(13), 1721–1726.
https://doi.org/10.1101/gad.1431006

Zaid, H., Rayan, A., Said, O., & Saad, B. (2010). Cancer Treatment by Greco-Arab and Islamic Herbal Medicine. In *The Open Nutraceuticals Journal* (Vol. 3).

Zellweger, R., Dalcher, D., Mutreja, K., Berti, M., Schmid, J. A., Herrador, R., Vindigni, A., & Lopes, M. (2015). Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. *Journal of Cell Biology*, 208(5), 563–579. https://doi.org/10.1083/jcb.201406099

Zeman, M. K., & Cimprich, K. A. (2014). Causes and consequences of replication stress. In *Nature Cell Biology* (Vol. 16, Issue 1, pp. 2–9). https://doi.org/10.1038/ncb2897

Zhang, J., Dai, Q., Park, D., & Deng, X. (2016). Targeting DNA replication stress for cancer therapy. In *Genes* (Vol. 7, Issue 8). MDPI AG. https://doi.org/10.3390/genes7080051

Zhao, H., & Piwnica-Worms, H. (2001). ATR-Mediated Checkpoint Pathways Regulate Phosphorylation and Activation of Human Chk1. *Molecular and Cellular Biology*, 21(13), 4129–4139.
https://doi.org/10.1128/MCB.21.13.4129-4139.2001

Zhao, L., & Washington, M. (2017). Translesion Synthesis: Insights into the Selection and Switching of DNA Polymerases. *Genes*, 8(1), 24. https://doi.org/10.3390/genes8010024

Zhao, M., Tan, B., Dai, X., Shao, Y., He, Q., Yang, B., Wang, J., & Weng, Q. (2019). DHFR/TYMS are positive regulators of glioma cell growth and modulate chemo-sensitivity to temozolomide. *European Journal of Pharmacology*, 863, 172665. https://doi.org/10.1016/j.ejphar.2019.172665

Zhi, G., Wilson, J. B., Chen, X., Krause, D. S., Xiao, Y., Jones, N. J., & Kupfer, G. M. (2009). Fanconi Anemia Complementation Group FANCD2 Protein Serine 331 Phosphorylation Is Important for Fanconi Anemia Pathway Function and BRCA2 Interaction. *Cancer Research*, 69(22), 8775–8783.
https://doi.org/10.1158/0008-5472.CAN-09-2312

Zhou, B.-B. S., & Elledge², S. J. (2000a). The DNA damage response: putting checkpoints in perspective. In *NATURE* (Vol. 408). www.nature.com433

Zhou, Y., Tao, L., Zhou, X., Zuo, Z., Gong, J., Liu, X., Zhou, Y., Liu, C., Sang, N., Liu, H., Zou, J., Gou, K., Yang, X., & Zhao, Y. (2021). DHODH and cancer: promising prospects to be explored. *Cancer & Metabolism*, 9(1). https://doi.org/10.1186/s40170-021-00250-z

Zhu, H., Swami, U., Preet, R., & Zhang, J. (2020). Harnessing dna replication stress for novel cancer therapy. In *Genes* (Vol. 11, Issue 9, pp. 1–20). MDPI AG. https://doi.org/10.3390/genes11090990

Zlotorynski, E., Rahat, A., Skaug, J., Ben-Porat, N., Ozeri, E., Hershberg, R., Levi, A., Scherer, S. W., Margalit, H., & Kerem, B. (2003). Molecular Basis for Expression of Common and Rare Fragile Sites. *Molecular and Cellular Biology*, 23(20), 7143–7151. https://doi.org/10.1128/MCB.23.20.7143-7151.2003

Zou, L., & Elledge, S. J. (2003). Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes. *Science*, 300(5625), 1542–1548. https://doi.org/10.1126/science.1083430

Zou, Y., Liu, Y., Wu, X., & Shell, S. M. (2006). Functions of human replication protein A (RPA): From DNA replication to DNA damage and stress responses. *Journal of Cellular Physiology*, 208(2), 267–273.
https://doi.org/10.1002/jcp.20622