Skip to main content
SpringerLink
Log in

Translesion DNA Synthesis and Reinitiation of DNA Synthesis in Chemotherapy Resistance

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Many chemotherapy drugs block tumor cell division by damaging DNA. DNA polymerases eta (Pol η), iota (Pol ι), kappa (Pol κ), REV1 of the Y-family and zeta (Pol ζ) of the B-family efficiently incorporate nucleotides opposite a number of DNA lesions during translesion DNA synthesis. Primase-polymerase PrimPol and the Pol α-primase complex reinitiate DNA synthesis downstream of the damaged sites using their DNA primase activity. These enzymes can decrease the efficacy of chemotherapy drugs, contribute to the survival of tumor cells and to the progression of malignant diseases. DNA polymerases are promising targets for increasing the effectiveness of chemotherapy, and mutations and polymorphisms in some DNA polymerases can serve as additional prognostic markers in a number of oncological disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

Notes

  1. * Xenograft – an experimental cancer model based on human tumor cells transplanted into animals (e.g., mice).

Abbreviations

HR:

hazard ratio

OR:

odds ratio

Pol:

DNA-polymerase

RIR:

REV1 interacting region

UBM2:

ubiquitin-binding motif 2

XP-V:

xeroderma pigmentosum variant

REFERENCES

  1. Burgers, P. M. J., and Kunkel, T. A. (2017) Eukaryotic DNA replication fork, Annu. Rev. Biochem., 86, 417-438, doi: https://doi.org/10.1146/annurev-biochem-061516-044709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kunkel, T. A. (2009) Evolving views of DNA replication (in)fidelity, Cold Spring Harb. Symp. Quant. Biol., 74, 91-101, doi: https://doi.org/10.1101/sqb.2009.74.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., and Ellenberger, T. (2006) DNA Repair and Mutagenesis. Second Edition, ASM Press, Washington (DC).

  4. Makarova, A. V., and Burgers, P. M. (2015) Eukaryotic DNA polymerase ζ, DNA Rep. (Amst), 29, 47-55, doi: https://doi.org/10.1016/j.dnarep.2015.02.012.

    Article  CAS  Google Scholar 

  5. Rizzo, A. A., and Korzhnev, D. M. (2019) The Rev1-Pol ζ translesion synthesis mutasome: structure, interactions and inhibition, Enzymes, 45, 139-181, doi: https://doi.org/10.1016/bs.enz.2019.07.001.5.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Sale, J. E., Lehmann, A. R., and Woodgate, R. (2012) Y-family DNA polymerases and their role in tolerance of cellular DNA damage, Nat. Rev. Mol. Cell Biol., 13, 141-152, doi: https://doi.org/10.1038/nrm3289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yang, W., and Woodgate, R. (2007) What a difference a decade makes: insights into translesion DNA synthesis, Proc. Natl. Acad. Sci. USA, 104, 15591-15598, doi: https://doi.org/10.1073/pnas.0704219104.

    Article  PubMed  Google Scholar 

  8. Guilliam, T. A., Jozwiakowski, S. K., Ehlinger, A., Barnes, R. P., Rudd, S. G., Bailey, L. J., Skehel, M., Eckert, K. A., Chazin, W. J., and Doherty, A. J. (2015) Human PrimPol is a highly error-prone polymerase regulated by single-stranded DNA binding proteins, Nucleic Acids Res., 43, 1056-1068, doi: https://doi.org/10.1093/nar/gku1321.

    Article  CAS  PubMed  Google Scholar 

  9. Martínez-Jiménez, M. I., Lahera, A., and Blanco, L. (2017) Human PrimPol activity is enhanced by RPA, Sci. Rep., 7, 783, doi: https://doi.org/10.1038/s41598-017-00958-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shilkin, E. S., Boldinova, E. O., Stolyarenko, A. D., Goncharova, R. I., Chuprov-Netochin, R. N., Khairullin, R. F., Smal, M. P., and Makarova, A. V. (2020) Translesion DNA synthesis and carcinogenesis, Biochemistry (Moscow), 85, 494-506, doi: https://doi.org/10.31857/S032097252004003X.

    Article  Google Scholar 

  11. Siddik, Z. H. (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance, Oncogene, 22, 7265-7279, doi: https://doi.org/10.1038/sj.onc.1206933.

    Article  CAS  PubMed  Google Scholar 

  12. Gately, D., and Howell, S. (1993) Cellular accumulation of the anticancer agent cisplatin: a review, Br. J. Cancer, 67, 1171-1176, doi: https://doi.org/10.1038/bjc.1993.221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhou, J., Kang, Y., Chen, L., Wang, H., Liu, J., Zeng, S., and Yu, L. (2020) The drug-resistance mechanisms of five platinum-based antitumor agents, Front. Pharmacol., 11, 1-17, doi: https://doi.org/10.3389/fphar.2020.00343.

    Article  Google Scholar 

  14. Bancroft, D. P., Lepre, C. A., and Lippard, S. J. (1990) Platinum-195 NMR kinetic and mechanistic studies of cis- and trans-diamminedichloroplatinum(II) binding to DNA, J. Am. Chem. Soc., 112, 6860-6871, doi: https://doi.org/10.1021/ja00175a020.

    Article  CAS  Google Scholar 

  15. Fichtinger-Schepman, A. M. J., Lohman, P. H. M., Berends, F., and van Oosterom, A. T. (1987) Cis-diamminedichloroplatinum(ii)-induced DNA adducts in peripheral leukocytes from seven cancer patients: quantitative immunochemical detection of the adduct induction and removal after a single dose of cis-diamminedichloroplatinum(ii), Cancer Res., 47, 3000-3004.

    CAS  PubMed  Google Scholar 

  16. Plooy, A. C. M., Fichtinger-Schepman, A. M. J., Schutte, H. H., Van Dijk, M., and Lohman, P. H. M. (1985) The quantitative detection of various Pt-DNA-adducts in chinese hamster ovary cells treated with cisplatin: application of immunochemical techniques, Carcinogenesis, 6, 561-566, doi: https://doi.org/10.1093/carcin/6.4.561.

    Article  CAS  PubMed  Google Scholar 

  17. Cummings, J., Spanswick, V. J., and Smyth, J. F. (1995) Re-evaluation of the molecular pharmacology of mitomycin C, Eur. J. Cancer, 31, 1928-1933, doi: https://doi.org/10.1016/0959-8049(95)00364-9.

    Article  Google Scholar 

  18. Tomasz, M., (1995) Mitomycin C: small, fast and deadly (but very selective), Chem. Biol., 2, 575-579, doi: https://doi.org/10.1016/1074-5521(95)90120-5.

    Article  CAS  PubMed  Google Scholar 

  19. Umar, G. S., Lipman, R., Cummings, J., and Tomasz, M. (1997) Mitomycin cDNA adducts generated by DT-diaphorase. revised mechanism of the enzymatic reductive activation of mitomycin C, Biochemistry, 36, 14128-14136, doi: https://doi.org/10.1021/bi971394i.

    Article  Google Scholar 

  20. Warren, A. J., Maccubbin, A. E., and Hamilton, J. W. (1998) Detection of mitomycin C DNA adducts in vivo by 32P-postlabeling: time course for formation and removal of adducts and biochemical modulation, Cancer Res., 58, 453-461.

    CAS  PubMed  Google Scholar 

  21. Tomasz, M., Lipman, R., Chowdary, D., Pawlak, J., Verdine, G., and Nakanishi, K. (1987) Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA, Science, 235, 1204-1208, doi: https://doi.org/10.1126/science.3103215.

    Article  CAS  PubMed  Google Scholar 

  22. Dong, Q., Barsky, D., Colvin, M. E., Melius, C. F., Ludeman, S. M., Moravek, J. F., Colvin, O. M., Bigner, D. D., Modrich, P., and Friedman, H. S. (1995) A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5′-d(GAC), Proc. Natl. Acad. Sci. USA, 92, 12170-12174, doi: https://doi.org/10.1073/pnas.92.26.12170.

    Article  CAS  PubMed  Google Scholar 

  23. Rink, S. M., Solomon, M. S., Taylor, M. J., Hopkins, P. B., Rajur, S. B., and McLaughlin, L. W. (1993) Covalent structure of a nitrogen mustard-induced DNA interstrand cross-link: an N7-to-N7 Linkage of deoxyguanosine residues at the duplex sequence 5′-d(GNC), J. Am. Chem. Soc., 115, 2551-2557, doi: https://doi.org/10.1021/ja00060a001.

    Article  CAS  Google Scholar 

  24. Rink, S. M., and Hopkins, P. B. (1995) A mechlorethamine-induced DNA interstrand cross-link Bends duplex DNA, Biochemistry, 34, 1439-1445, doi: https://doi.org/10.1021/bi00004a039.

    Article  CAS  PubMed  Google Scholar 

  25. Brandes, A. A., Bartolotti, M., Tosoni, A., and Franceschi, E. (2016) Nitrosoureas in the management of malignant gliomas, Curr. Neurol. Neurosci. Rep., 16, 13, doi: https://doi.org/10.1007/s11910-015-0611-8.

    Article  CAS  PubMed  Google Scholar 

  26. Nikolova, T., Roos, W. P., Krämer, O. H., Strik, H. M., and Kaina, B. (2017) Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling, Biochim. Biophys. Acta Rev. Cancer, 1868, 29-39, doi: https://doi.org/10.1016/j.bbcan.2017.01.004.

    Article  CAS  PubMed  Google Scholar 

  27. Chen, F. X., Bodell, W. J., Liang, G., and Gold, B. (1996) Reaction of N-(2-chloroethyl)-N-nitrosoureas with DNA: effect of buffers on DNA adduction, cross-linking, and cytotoxicity, Chem. Res. Toxicol., 9, 208-214, doi: https://doi.org/10.1021/tx950097g.

    Article  CAS  PubMed  Google Scholar 

  28. Denny, B. J., Tsang, L. L. H., Slack, J. A., Wheelhouse, R. T., and Stevens, M. F. G. (1994) NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA, Biochemistry, 33, 9045-9051, doi: https://doi.org/10.1021/bi00197a003.

    Article  CAS  PubMed  Google Scholar 

  29. Friedman, H. S., Kerby, T., and Calvert, H. (2000) Temozolomide and treatment of malignant glioma, Clin. Cancer Res., 6, 2585-2597.

    CAS  PubMed  Google Scholar 

  30. Tentori, L., and Graziani, G. (2002) Pharmacological strategies to increase the antitumor activity of methylating agents, Curr. Med. Chem., 9, 1285-1301, doi: https://doi.org/10.2174/0929867023369916.

    Article  CAS  PubMed  Google Scholar 

  31. Tsesmetzis, N., Paulin, C. B. J., Rudd, S. G., and Herold, N. (2018) Nucleobase and nucleoside analogues: resistance and re-sensitisation at the level of pharmacokinetics, pharmacodynamics and metabolism, Cancers (Basel), 10, 240, doi: https://doi.org/10.3390/cancers10070240.

    Article  CAS  Google Scholar 

  32. Berdis, A. J. (2017) Inhibiting DNA polymerases as a therapeutic intervention against cancer, Front. Mol. Biosci., 4, 1-12, doi: https://doi.org/10.3389/fmolb.2017.00078.

    Article  CAS  Google Scholar 

  33. Mini, E., Nobili, S., Caciagli, B., Landini, I., and Mazzei, T. (2006) Cellular pharmacology of gemcitabine, Ann. Oncol., 17, 7-12, doi: https://doi.org/10.1093/annonc/mdj941.

    Article  Google Scholar 

  34. Liang, X., Wu, Q., Luan, S., Yin, Z., He, C., Yin, L., Zou, Y., Yuan, Z., Li, L., Song, X., He, M., Lv, C., and Zhang, W. (2019) A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade, Eur. J. Med. Chem., 171, 129-168, doi: https://doi.org/10.1016/j.ejmech.2019.03.034.

    Article  CAS  PubMed  Google Scholar 

  35. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., and Gianni, L. (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity, Pharmacol. Rev., 56, 185-229, doi: https://doi.org/10.1124/pr.56.2.6.

    Article  CAS  PubMed  Google Scholar 

  36. Masutani, C., Kusumoto, R., Yamada, A., Dohmae, N., Yokoi, M., Yuasa, M., Araki, M., Iwai, S., Takio, K., and Hanaoka, F. (1999) The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta, Nature, 399, 700-704, doi: https://doi.org/10.1038/21447.

    Article  CAS  PubMed  Google Scholar 

  37. Alt, A., Lammens, K., Chiocchini, C., Lammens, A., Pieck, J. C., Kuch, D., Hopfner, K. P., and Carell, T. (2007) Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta, Science, 318, 967-970, doi: https://doi.org/10.1126/science.1148242.

    Article  CAS  PubMed  Google Scholar 

  38. Ouzon-Shubeita, H., Baker, M., Koag, M.-C., and Lee, S. (2019) Structural basis for the bypass of the major oxaliplatin-DNA adducts by human DNA polymerase η, Biochem. J., 476, 747-758, doi: https://doi.org/10.1042/BCJ20180848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ummat, A., Rechkoblit, O., Jain, R., Roy Choudhury, J., Johnson, R. E., Silverstein, T. D., Buku, A., Lone, S., Prakash, L., Prakash, S., and Aggarwal, A. K. (2012) Structural basis for cisplatin DNA damage tolerance by human polymerase η during cancer chemotherapy, Nat. Struct. Mol. Biol., 19, 628-632, doi: https://doi.org/10.1038/nsmb.2295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Vaisman, A., Masutani, C., Hanaoka, F., and Chaney, S. G. (2000) Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase eta, Biochemistry, 39, 4575-4580, doi: https://doi.org/10.1021/bi000130k.

    Article  CAS  PubMed  Google Scholar 

  41. Zhao, Y., Biertümpfel, C., Gregory, M. T., Hua, Y. J., Hanaoka, F., and Yang, W. (2012) Structural basis of human DNA polymerase η-mediated chemoresistance to cisplatin, Proc. Natl. Acad. Sci. USA, 109, 7269-7274, doi: https://doi.org/10.1073/pnas.1202681109.

    Article  PubMed  Google Scholar 

  42. Shachar, S., Ziv, O., Avkin, S., Adar, S., Wittschieben, J., Reissner, T., Chaney, S., Friedberg, E. C., Wang, Z., Carell, T., Geacintov, N., and Livneh, Z. (2009) Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals, EMBO J., 28, 383-393, doi: https://doi.org/10.1038/emboj.2008.281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Srivastava, A. K., Han, C., Zhao, R., Cui, T., Dai, Y., Mao, C., Zhao, W., Zhang, X., Yu, J., and Wang, Q. E. (2015) Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells, Proc. Natl. Acad. Sci. USA, 112, 4411-4416.

    Article  CAS  Google Scholar 

  44. Li, X.-Q., Ren, J., Chen, P., Chen, Y.-J., Wu, M., Wu, Y., Chen, K., and Li, J. (2018) Co-inhibition of Pol η and ATR sensitizes cisplatin-resistant non-small cell lung cancer cells to cisplatin by impeding DNA damage repair, Acta Pharmacol. Sin., 39, 1359-1372, doi: https://doi.org/10.1038/aps.2017.187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang, J., Sun, W., Ren, C., Kong, X., Yan, W., and Chen, X. (2019) A PolH transcript with a short 3′UTR enhances PolH expression and mediates cisplatin resistance, Cancer Res., 79, 3714-3724, doi: https://doi.org/10.1158/0008-5472.CAN-18-3928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ceppi, P., Novello, S., Cambieri, A., Longo, M., Monica, V., Iacono, M. L., Giaj-Levra, M., Saviozzi, S., Volante, M., and Papotti, M. (2009) Polymerase eta mRNA expression predicts survival of non-small cell lung cancer patients treated with platinum-based chemotherapy, Clin. Cancer Res., 15, 1039-1045, doi: https://doi.org/10.1158/1078-0432.CCR-08-1227.

    Article  CAS  PubMed  Google Scholar 

  47. Teng, K., Qiu, M., Li, Z., Luo, H., Zeng, Z., Luo, R., Zhang, H., Wang, Z., Li, Y., and Xu, R. (2010) DNA polymerase η protein expression predicts treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy, J. Transl. Med., 8, 126, doi: https://doi.org/10.1186/1479-5876-8-126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Albertella, M. R., Green, C. M., Lehmann, A. R., and O’Connor, M. J. (2005) A role for polymerase η in the cellular tolerance to cisplatin-induced damage, Cancer Res., 65, 9799-806, doi: https://doi.org/10.1158/0008-5472.CAN-05-1095.

    Article  CAS  PubMed  Google Scholar 

  49. Sumiyoshi, M., Soda, H., Sadanaga, N., Taniguchi, H., Ikeda, T., Maruta, H., Dotsu, Y., Ogawara, D., Fukuda, Y., and Mukae, H. (2017) Alert regarding cisplatin-induced severe adverse events in cancer patients with xeroderma pigmentosum, Intern. Med., 56, 979-982, doi: https://doi.org/10.2169/internalmedicine.56.7866.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chen, Y.-W., Cleaver, J. E., Hanaoka, F., Chang, C.-F., and Chou, K.-M. (2006) A novel role of DNA polymerase eta in modulating cellular sensitivity to chemotherapeutic agents, Mol. Cancer Res., 4, 257-265, doi: https://doi.org/10.1158/1541-7786.MCR-05-0118.

    Article  CAS  PubMed  Google Scholar 

  51. Rechkoblit, O., Choudhury, J. R., Buku, A., Prakash, L., Prakash, S., and Aggarwal, A. K. (2018) Structural basis for polymerase η-promoted resistance to the anticancer nucleoside analog cytarabine, Sci. Rep., 8, 12702, doi: https://doi.org/10.1038/s41598-018-30796-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rechkoblit, O., Johnson, R. E., Buku, A., Prakash, L., Prakash, S., and Aggarwal, A. K. (2019) Structural insights into mutagenicity of anticancer nucleoside analog cytarabine during replication by DNA polymerase η, Sci. Rep., 9, 16400, doi: https://doi.org/10.1038/s41598-019-52703-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yoon, J.-H., Choudhury, R. J., Prakash, L., and Prakash, S. (2019) Translesion synthesis DNA polymerases η, ι, and υ promote mutagenic replication through the anticancer nucleoside cytarabine, J. Biol. Chem., 294, 19048-19054, doi: https://doi.org/10.1074/jbc.RA119.011381.

    Article  CAS  PubMed  Google Scholar 

  54. Yasui, M., Suzuki, N., Laxmi, Y. S., and Shibutani, S. (2006) Translesion synthesis past tamoxifen-derived DNA adducts by human DNA polymerases eta and kappa, Biochemistry, 45, 12167-12174, doi: https://doi.org/10.1021/bi0608461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. McDonald, J. P., Rapić-Otrin, V., Epstein, J. A., Broughton, B. C., Wang, X., Lehmann, A. R., Wolgemuth, D. J., and Woodgate, R. (1999) Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta, Genomics, 60, 20-30, doi: https://doi.org/10.1006/geno.1999.5906.

    Article  CAS  PubMed  Google Scholar 

  56. Smith, L. A., Makarova, A. V., Samson, L., Thiesen, K. E., Dhar, A., and Bessho, T. (2012) Bypass of a psoralen DNA interstrand cross-link by DNA polymerases β, ι, and κ in vitro, Biochemistry, 51, 8931-8938, doi: https://doi.org/10.1021/bi3008565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Minko, I. G., Harbut, M. B., Kozekov, I. D., Kozekova, A., Jakobs, P. M., Olson, S. B., Moses, R. E., Harris, T. M., Rizzo, C. J., and Lloyd, R. S. (2008) Role for DNA polymerase kappa in the processing of N2-N2-guanine interstrand cross-links, J. Biol. Chem., 283, 17075-17082, doi: https://doi.org/10.1074/jbc.M801238200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ho, V., Guainazzi, A., Derkunt, S. B., Enoiu, M., and Schärer, O. D. (2011) Structure-dependent bypass of DNA interstrand crosslinks by translesion synthesis polymerases, Nucleic Acids Res., 39, 7455-7464, doi: https://doi.org/10.1093/nar/gkr448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jha, V., and Ling, H. (2018) Structural basis for human DNA polymerase kappa to bypass cisplatin intrastrand cross-link (Pt-GG) lesion as an efficient and accurate extender, J. Mol. Biol., 430, 1577-1589, doi: https://doi.org/10.1016/j.jmb.2018.04.023.

    Article  CAS  PubMed  Google Scholar 

  60. Kanemaru, Y., Suzuki, T., Sassa, A., Matsumoto, K., Adachi, N., Honma, M., Numazawa, S., and Nohmi, T. (2017) DNA polymerase kappa protects human cells against MMC-induced genotoxicity through error-free translesion DNA synthesis, Genes Environ., 39, 6, doi: https://doi.org/10.1186/s41021-016-0067-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Takeiri, A., Wada, N. A., Motoyama, S., Matsuzaki, K., Tateishi, H., Matsumoto, K., Niimi, N., Sassa, A., Grúz, P., Masumura, K., Yamada, M., Mishima, M., Jishage, K. I., and Nohmi, T. (2014) In vivo evidence that DNA polymerase kappa is responsible for error-free bypass across DNA cross-links induced by mitomycin C, DNA Rep., 24, 113-121, doi: https://doi.org/10.1016/j.dnarep.2014.09.002.

    Article  CAS  Google Scholar 

  62. Williams, H. L., Gottesman, M. E., and Gautier, J. (2012) Replication-independent repair of DNA interstrand crosslinks, Mol. Cell, 47, 140-147, doi: https://doi.org/10.1016/j.molcel.2012.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhuo, M., Gorgun, M. F., and Englander, E. W. (2018) Translesion synthesis DNA polymerase kappa is indispensable for DNA repair synthesis in cisplatin exposed dorsal root ganglion neurons, Mol. Neurobiol., 55, 2506-2515, doi: https://doi.org/10.1007/s12035-017-0507-5.

    Article  CAS  PubMed  Google Scholar 

  64. Shao, M., Jin, B., Niu, Y., Ye, J., Lu, D., and Han, B. (2014) Association of POLK polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients, Cell Biochem. Biophys., 70, 1227-1237, doi: https://doi.org/10.1007/s12013-014-0046-x.

    Article  CAS  PubMed  Google Scholar 

  65. Goričar, K., Kovač, V., and Dolžan, V. (2014) Polymorphisms in translesion polymerase genes influence treatment outcome in malignant mesothelioma, Pharmacogenomics, 15, 941-950, doi: https://doi.org/10.2217/pgs.14.14.

    Article  CAS  PubMed  Google Scholar 

  66. Ye, J., Chu, T., Li, R., Niu, Y., Jin, B., Xia, J., Shao, M., and Han, B. (2015) Pol ζ polymorphisms are associated with platinum based chemotherapy response and side effects among non-small cell lung cancer patients, Neoplasma, 62, 833-839, doi: https://doi.org/10.4149/neo_2015_101.

    Article  CAS  PubMed  Google Scholar 

  67. Goričar, K., Kovač, V., Jazbec, J., Zakotnik, B., Lamovec, J., and Dolžan, V. (2015) Translesion polymerase genes polymorphisms and haplotypes influence survival of osteosarcoma patients, OMICS, 19, 180-185, doi: https://doi.org/10.1089/omi.2014.0159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zheng, Y., Deng, Z., Yin, J., Wang, S., Lu, D., Wen, X., Li, X., Xiao, D., Hu, C., Chen, X., Zhang, W., Zhou, H., and Liu, Z. (2017) The association of genetic variations in DNA repair pathways with severe toxicities in NSCLC patients undergoing platinum-based chemotherapy, Int. J. Cancer, 141, 2336-2347, doi: https://doi.org/10.1002/ijc.30921.

    Article  CAS  PubMed  Google Scholar 

  69. Wang, J., Wang, X., Zhao, M., Choo, S. P., Ong, S. J., Ong, S. Y., Chong, S. S., Teo, Y. Y., and Lee, C. G. (2014) Potentially functional SNPs (pfSNPs) as novel genomic predictors of 5-FU response in metastatic colorectal cancer patients, PLoS One, 9, e111694, doi: https://doi.org/10.1371/journal.pone.0111694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Huang, K. K., Jang, K. W., Kim, S., Kim, H. S., Kim, S.-M., Kwon, H. J., Kim, H. R., Yun, H. J., Ahn, M. J., and Park, K. U. (2016) Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck, Sci. Rep., 6, 19552, doi: https://doi.org/10.1038/srep19552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Xu, H. L., Gao, X. R., Zhang, W., Cheng, J. R., Tan, Y. T., Zheng, W., Shu, X. O., and Xiang, Y. B. (2013) Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men, Cancer Epidemiol., 37, 917-922, doi: https://doi.org/10.1016/j.canep.2013.08.003.

    Article  PubMed  Google Scholar 

  72. Baranovskiy, A. G., Lada, A. G., Siebler, H. M., Zhang, Y., Pavlov, Y. I., and Tahirov, T. H. (2012) DNA polymerase δ and ζ switch by sharing accessory subunits of DNA polymerase δ, J. Biol. Chem., 287, 17281-17287, doi: https://doi.org/10.1074/jbc.M112.351122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Lee, Y. S., Gregory, M. T., and Yang, W. (2014) Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass, Proc. Natl. Acad. Sci. USA, 111, 2954-2959, doi: https://doi.org/10.1073/pnas.1324001111.

    Article  CAS  PubMed  Google Scholar 

  74. Makarova, A. V., Stodola, J. L., and Burgers, P. M. (2012) A four-subunit DNA polymerase ζ complex containing Pol δ accessory subunits is essential for PCNA-mediated mutagenesis, Nucleic Acids Res., 40, 11618-11626, doi: https://doi.org/10.1093/nar/gks948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Rizzo, A. A., Vassel, F.-M., Chatterjee, N., D’Souza, S., Li, Y., Hao, B., Hemann, M. T., Walker, G. C., and Korzhnev, D. M. (2018) Rev7 dimerization is important for assembly and function of the Rev1/Polζ translesion synthesis complex, Proc. Natl. Acad. Sci. USA, 115, 8191-8200, doi: https://doi.org/10.1073/pnas.1801149115.

    Article  CAS  Google Scholar 

  76. Adachi, M., Ijichi, K., Hasegawa, Y., Ogawa, T., Nakamura, H., Yasui, Y., Fukushima, M., and Ishizaki, K. (2008) Hypersensitivity to cisplatin after hRev3 mRNA knockdown in head and neck squamous cell carcinoma cells, Mol. Med. Rep., 1, 695-698, doi: https://doi.org/10.3892/mmr_00000015.

    Article  CAS  PubMed  Google Scholar 

  77. Chen, X., Zhu, H., Ye, W., Cui, Y., and Chen, M. (2019) MicroRNA-29a enhances cisplatin sensitivity in non-small cell lung cancer through the regulation of REV3L, Mol. Med. Rep., 19, 831-840, doi: https://doi.org/10.3892/mmr.2018.9723.

    Article  CAS  PubMed  Google Scholar 

  78. Lin, X., Trang, J., Okuda, T., Stephen, B., and Howell, S. B. (2006) DNA polymerase zeta accounts for the reduced cytotoxicity and enhanced mutagenicity of cisplatin in human colon carcinoma cells that have lost DNA mismatch repair, Clin. Cancer Res., 12, 563-568, doi: https://doi.org/10.1158/1078-0432.CCR-05-1380.

    Article  CAS  PubMed  Google Scholar 

  79. Song, L., McNeil, E. M., Ritchie, A.-M., Astell, K. R., Gourley, C., and Melton, D. W. (2017) Melanoma cells replicate through chemotherapy by reducing levels of key homologous recombination protein RAD51 and increasing expression of translesion synthesis DNA polymerase ζ, BMC Cancer, 17, 864, doi: https://doi.org/10.1186/s12885-017-3864-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wang, H., Zhang, S.-Y., Wang, S, Lu, J., Wu, W., Weng, L., Chen, D., Zhang, Y., Lu, Z., Yang, J., Chen, Y., Zhang, X., Chen, X., Xi, C., Lu, D., and Zhao, S. (2009) REV3L confers chemoresistance to cisplatin in human gliomas: the potential of its RNAi for synergistic therapy, Neuro Oncol., 11, 790-802, doi: https://doi.org/10.1215/15228517-2009-015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wang, W., Sheng, W., Yu, C., Cao, J., Zhou, J., Wu, J., Zhang, H., and Zhang, S. (2015) REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells, Oncol. Rep., 34, 1460-1468, doi: https://doi.org/10.3892/or.2015.4121.

    Article  CAS  PubMed  Google Scholar 

  82. Wu, F., Lin, X., Okuda, T., and Howell, S. B. (2004) DNA polymerase zeta regulates cisplatin cytotoxicity, mutagenicity, and the rate of development of cisplatin resistance, Cancer Res., 64, 8029-8035, doi: https://doi.org/10.1158/0008-5472.CAN-03-3942.

    Article  CAS  PubMed  Google Scholar 

  83. Zhu, X., Zou, S., Zhou, J., Zhu, H., Zhang, S., Shang, Z., Ding, W.-Q., Wu, J., and Chen, Y. (2016) REV3L, the catalytic subunit of DNA polymerase ζ, is involved in the progression and chemoresistance of esophageal squamous cell carcinoma, Oncol. Rep., 35, 1664-1670, doi: https://doi.org/10.3892/or.2016.4549.

    Article  CAS  PubMed  Google Scholar 

  84. Roos, W. P., Tsaalbi-Shtylik, A., Tsaryk, R., Güvercin, F., de Wind, N., and Kaina, B. (2009) The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs, Mol. Pharmacol., 76, 927-934, doi: https://doi.org/10.1124/mol.109.058131.

    Article  CAS  PubMed  Google Scholar 

  85. Doles, J., Oliver, T. G., Cameron, E. R., Hsu, G., Jacks, T., Walker, G. C., and Hemann, M. T. (2010) Suppression of Rev3, the catalytic subunit of pol zeta, sensitizes drug-resistant lung tumors to chemotherapy, Proc. Natl. Acad. Sci. USA, 107, 20786-20791, doi: https://doi.org/10.1073/pnas.1011409107.

    Article  PubMed  Google Scholar 

  86. Yang, L., Shi, T., Liu, F., Ren, C., Wang, Z., Li, Y., Tu, X., Yang, G., and Cheng, X. (2015) REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells, PLoS One, 10, e0120334, doi: https://doi.org/10.1371/journal.pone.0120334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Xie, K., Doles, J., Hemann, M. T., and Walker, G. C. (2010) Error-prone translesion synthesis mediates acquired chemoresistance, Proc. Natl. Acad. Sci. USA, 107, 20792-20797, doi: https://doi.org/10.1073/pnas.1011412107.

    Article  CAS  PubMed  Google Scholar 

  88. Gu, C., Luo, J., Lu, X., Tang, Y., Ma, Y., Yun, Y., Cao, J., Cao, J., Huang, Z., and Zhou, X. (2019) REV7 confers radioresistance of esophagus squamous cell carcinoma by recruiting PRDX2, Cancer Sci., 110, 962, doi: https://doi.org/10.1111/cas.13946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Okina, S., Yanagisawa, N., Yokoyama, M., Sakurai, Y., Numata, Y., Umezawa, A., Higashihara, M., and Murakumo, Y. (2015) High expression of REV7 is an independent prognostic indicator in patients with diffuse large B-cell lymphoma treated with rituximab, Int. J. Hematology, 102, 662-669, doi: https://doi.org/10.1007/s12185-015-1880-3.

    Article  CAS  Google Scholar 

  90. Masuda, Y., and Kamiya, K. (2002) Biochemical properties of the human REV1 protein, FEBS Lett., 520, 88-92, doi: https://doi.org/10.1016/s0014-5793(02)02773-4.

    Article  CAS  PubMed  Google Scholar 

  91. Choi, J. Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F. P. (2010) Translesion synthesis across abasic lesions by human B-family and Y-family DNA polymerases α, δ, η, ι, κ, and REV1, J. Mol. Biol., 404, 34-44, doi: https://doi.org/10.1016/j.jmb.2010.09.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Choi, J. Y., and Guengerich, F. P. (2008) Kinetic analysis of translesion synthesis opposite bulky N2- and O6-alkylguanine DNA adducts by human DNA polymerase REV1, J. Biol. Chem., 283, 23645-23655, doi: https://doi.org/10.1074/jbc.M801686200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lin, X., Okuda, T., Trang, J., and Howell, S. B. (2006) Human REV1 modulates the cytotoxicity and mutagenicity of cisplatin in human ovarian carcinoma cells, Mol. Pharmacol., 69, 1748-1754, doi: https://doi.org/10.1124/mol.105.020446.

    Article  CAS  PubMed  Google Scholar 

  94. Okuda, T., Lin, X., Trang, J., and Howell, S. B. (2005) Suppression of hREV1 expression reduces the rate at which human ovarian carcinoma cells acquire resistance to cisplatin, Mol. Pharmacol., 67, 1852-1860, doi: https://doi.org/10.1124/mol.104.010579.

    Article  CAS  PubMed  Google Scholar 

  95. Rusz, O., Pál, M., Szilágyi, É., Rovó, L., Varga, Z., Tomisa, B., Fábián, G., Kovács, L., Nagy, O., Mózes, P., Reisz, Z., Tiszlavicz, L., Deák, P., and Kahán, Z. (2017) The expression of checkpoint and DNA repair genes in head and neck cancer as possible predictive factors, Pathol. Oncol. Res., 23, 253-264, doi: https://doi.org/10.1007/s12253-016-0088-z.

    Article  CAS  PubMed  Google Scholar 

  96. Actis, M. L., Ambaye, N. D., Evison, B. J., Shao, Y., Vanarotti, M., Inoue, A., McDonald, E. T., Kikuchi, S., Heath, R., Hara, K., Hashimoto, H., and Fujii, N. (2016) Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction, Bioorg. Med. Chem., 24, 4339-4346, doi: https://doi.org/10.1016/j.bmc.2016.07.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Coggins, G. E., Maddukuri, L., Penthala, N. R., Hartman, J. H., Eddy, S., Ketkar, A., Crooks, P. A., and Eoff, R. L. (2013) N-aroyl indole thiobarbituric acids as inhibitors of DNA repair and replication stress response polymerases, ACS Chem. Biol., 8, 1722-1729, doi: https://doi.org/10.1021/cb400305r.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Dash, R. C., Ozen, Z., McCarthy, K. R., Chatterjee, N., Harris, C. A., Rizzo, A. A., Walker, G. C., Korzhnev, D. M., and Hadden, M. K. (2019) Virtual pharmacophore screening identifies small-molecule inhibitors of the Rev1-CT/RIR protein–protein interaction, Chem. Med. Chem., 14, 1610-1617, doi: https://doi.org/10.1002/cmdc.201900307.

    Article  CAS  PubMed  Google Scholar 

  99. Dash, R. C., Ozen, Z., Rizzo, A. A., Lim, S., Korzhnev, D. M., and Hadden, M. K. (2018) Structural approach to identify a lead scaffold that targets the translesion synthesis polymerase Rev1, J. Chem. Inf. Model., 58, 2266-2277, doi: https://doi.org/10.1021/acs.jcim.8b00535.

    Article  CAS  PubMed  Google Scholar 

  100. Ozen, Z., Dash, R. C., McCarthy, K. R., Chow, S. A., Rizzo, A. A., Korzhnev, D. M., and Hadden, M. K. (2018) Small molecule scaffolds that disrupt the Rev1-CT/RIR protein–protein interaction, Bioorg. Med. Chem., 26, 4301-4309, doi: https://doi.org/10.1016/j.bmc.2018.07.029.

    Article  CAS  PubMed  Google Scholar 

  101. Sail, V., Rizzo, A. A., Chatterjee, N., Dash, R. C., Ozen, Z., Walker, G. C., Korzhnev, D. M., and Hadden, M. K. (2017) Identification of small molecule translesion synthesis inhibitors that target the Rev1-CT/RIR protein−protein interaction, ACS Chem. Biol., 12, 1903-1912, doi: https://doi.org/10.1021/acschembio.6b01144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Vanarotti, M., Evison, B. J., Actis, M. L., Inoue, A., McDonald, E. T., Shao, Y., Heath, R. J., and Fujiia, N. (2018) Small-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1 interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance, Bioorg. Med. Chem., 26, 2345-2353, doi: https://doi.org/10.1016/j.bmc.2018.03.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wojtaszek, J. L., Chatterjee, N., Najeeb, J., Ramos, A., Lee, M., Bian, K., Xue, J. Y., Fenton, B. A., Park, H., Li, D., Hemann, M. T., Hong, J., Walker, G. C., and Zhou, P. (2019) A small molecule targeting mutagenic translesion synthesis improves chemotherapy, Cell, 178, 152-159, doi: https://doi.org/10.1016/j.cell.2019.05.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Yamanaka, K., Dorjsuren, D., Eoff, R. L., Egli, M., Maloney, D. J., Jadhav, A., Simeonov, A., Stephen, R., and Lloyd, R. S. (2012) A comprehensive strategy to discover inhibitors of the translesion synthesis DNA polymerase κ, PLoS One, 7, e45032, doi: https://doi.org/10.1371/journal.pone.0045032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Zafar, M. K., Maddukuri, L., Ketkar, A., Penthala, N. R., Reed, M. R., Eddy, S., Crooks, P. A., and Eoff, R. L. (2018) A small-molecule inhibitor of human DNA polymerase η potentiates the effects of cisplatin in tumor cells, Biochemistry, 57, 1262-1273, doi: https://doi.org/10.1021/acs.biochem.7b01176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Dumstorf, C. A., Mukhopadhyay, S., Krishnan, E., Haribabu, B., and McGregor, W. G. (2009) REV1 is implicated in the development of carcinogen-induced lung cancer, Mol. Cancer Res., 7, 247-254, doi: https://doi.org/10.1158/1541-7786.MCR-08-0399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Lakhin, A. V., Kazakov, A. A., Makarova, A. V., Pavlov, Y. I., Efremova, A. S., Shram, S. I., Tarantul, V. Z., and Gening, L. V. (2012) Isolation and characterization of high affinity aptamers against DNA polymerase iota, Nucleic Acids Ther., 22, 49-57, doi: https://doi.org/10.1089/nat.2011.0324.

    Article  CAS  Google Scholar 

  108. Zafar, M. K., and Eoff, R. L. (2017) Translesion DNA synthesis in cancer: molecular mechanisms and therapeutic opportunities, Chem. Res. Toxicol., 30, 1942-1955, doi: https://doi.org/10.1021/acs.chemrestox.7b00157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Choi, J.-S., Kim, S., Motea, E., and Berdis, A. (2017) Inhibiting translesion DNA synthesis as an approach to combat drug resistance to DNA damaging agents, Oncotarget, 20, 40804-40816, doi: https://doi.org/10.18632/oncotarget.17254.

    Article  Google Scholar 

  110. García-Gómez, S., Reyes, A., Martínez-Jiménez, M. I., Chocrón, E. S., Mourón, S., Terrados, G., Powell, C., Salido, E., Méndez, J., Holt, I. J., and Blanco, L. (2013) PrimPol, an archaic primase/polymerase operating in human cells, Mol. Cell, 52, 541-553, doi: https://doi.org/10.1016/j.molcel.2013.09.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bianchi, J., Rudd, S. G., Jozwiakowski, S. K., Bailey, L. J., Soura, V., Taylor, E., Stevanovic, I., Green, A. J., Stracker, T. H., Lindsay, H. D., and Doherty, A. J. (2013) PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication, Mol. Cell, 52, 566-573, doi: https://doi.org/10.1016/j.molcel.2013.10.035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Kobayashi, K., Guilliam, T. A., Tsuda, M., Yamamoto, J., Bailey, L. J., Iwai, S., Takeda, S., Doherty, A. J., and Hirota, K. (2016) Repriming by PrimPol is critical for DNA replication restart downstream of lesions and chain-terminating nucleosides, Cell Cycle, 15, 1997-2008, doi: https://doi.org/10.1080/15384101.2016.1191711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Quinet, A., Tirman, S., Jackson, J., Šviković, S., Lemaçon, D., Carvajal-Maldonado, D., González-Acosta, D., Vessoni, A. T., Cybulla, E., Wood, M., Tavis, S., Batista, L. F. Z., Méndez, J., Sale, J. E., and Vindigni, A. (2020) PRIMPOL-mediated adaptive response suppresses replication fork reversal in BRCA-deficient cells, Mol. Cell, 77, 461-474, doi: https://doi.org/10.1016/j.molcel.2019.10.008.

    Article  CAS  PubMed  Google Scholar 

  114. Hatano, Y., Tamada, M., Matsuo, M., and Hara, A. (2020) Molecular trajectory of BRCA1 and BRCA2 mutations, Front. Oncol., 10, 361, doi: https://doi.org/10.3389/fonc.2020.00361.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Tokarsky, E. J., Wallenmeyer, P. C., Phi, K. K., and Suo, Z. (2017) Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human primPol, DNA Rep., 49, 51-59, doi: https://doi.org/10.1016/j.dnarep.2016.11.003.

    Article  CAS  Google Scholar 

  116. Liu, J., Lee, W., Jiang, Z., Chen, Z., Jhunjhunwala, S., Haverty, P. M., Gnad, F., Guan, Y., Gilbert, H. N., Stinson, J., Klijn, C., Guillory, J., Bhatt, D., Vartanian, S., Walter, K., Chan, J., Holcomb, T., Dijkgraaf, P., Johnson, S., Koeman, J., Minna, J. D., Gazdar, A. F., Stern, H. M., Hoeflich, K. P., Wu, T. D., Settleman, J., de Sauvage, F. J., Gentleman, R. C., Neve, R. M., Stokoe, D., Modrusan, Z., Seshagiri, S., Shames, D. S., and Zhang, Z. (2012) Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events, Genome Res., 22, 2315-2327, doi: https://doi.org/10.1101/gr.140988.112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Díaz-Talavera, A., Calvo, P. A., González-Acosta, D., Díaz, M., Sastre-Moreno, G., Blanco-Franco, L., Guerra, S., Martínez-Jiménez, M. I., Méndez, J., and Blanco, L. (2019) A cancer-associated point mutation disables the steric gate of human PrimPol, Sci. Rep., 9, 1121, doi: https://doi.org/10.1038/s41598-018-37439-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Taylor, M. R. G., and Yeeles, J. T. P. (2018) The initial response of a eukaryotic replisome to DNA damage, Mol. Cell, 70, 1067-1080, doi: https://doi.org/10.1016/j.molcel.2018.04.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Lopes, M., Foiani, M., and Sogo, J. M. (2006) Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions, Mol. Cell, 21, 15-27, doi: https://doi.org/10.1016/j.molcel.2005.11.015.

    Article  CAS  PubMed  Google Scholar 

  120. Svoboda, D. L., and Vos, J. M. (1995) Differential replication of a single, UV-induced lesion in the leading or lagging strand by a human cell extract: fork uncoupling or gap formation, Proc. Natl. Acad. Sci. USA, 92, 11975-11979, doi: https://doi.org/10.1073/pnas.92.26.11975.

    Article  CAS  PubMed  Google Scholar 

  121. Veaute, X., Mari-Giglia, G., Lawrence, C. W., and Sarasin, A. (2000) UV lesions located on the leading strand inhibit DNA replication but do not inhibit SV40 T-antigen helicase activity, Mutat. Res., 459, 19-28, doi: https://doi.org/10.1016/s0921-8777(99)00052-x.

    Article  CAS  PubMed  Google Scholar 

  122. Elvers, I., Johansson, F., Groth, P., Erixon, K., and Helleday, T. (2011) UV stalled replication forks restart by re-priming in human fibroblasts, Nucleic Acids Res., 39, 7049-7057, doi: https://doi.org/10.1093/nar/gkr420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Hedglin, M., and Benkovic, S. J. (2017) Eukaryotic translesion DNA synthesis on the leading and lagging strands: unique detours around the same obstacle, Chem. Rev., 117, 7857-7877, doi: https://doi.org/10.1021/acs.chemrev.7b00046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Schiavone, D., Jozwiakowski, S. K., Romanello, M., Guilbaud, G., Guilliam, T. A., Bailey, L. J., Sale, J. E., and Doherty, A. J. (2016) PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells, Mol. Cell, 61, 161-169, doi: https://doi.org/10.1016/j.molcel.2015.10.038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Pilzecker, B., Buoninfante, O. A., Pritchard, C., Blomberg, O. S., Huijbers, I. J., van den Berk, P. C. M., and Jacobs, H. (2016) PrimPol prevents APOBEC/AID family mediated DNA mutagenesis, Nucleic Acids Res., 44, 4734-4744, doi: https://doi.org/10.1093/nar/gkw123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Han, T., Goralski, M., Capota, E., Padrick, S. B., Kim, J., Xie, Y., and Nijhawan, D. (2016) The anti-tumor toxin CD437 is a direct inhibitor of DNA polymerase α, Nat. Chem. Biol., 12, 511-515, doi: https://doi.org/10.1038/nchembio.2082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Abdel-Samad, R., Aouad, P., Gali-Muhtasib, H., Sweidan, Z., Hmadi, R., Kadara, H., D’Andrea, E. L., Fucci, A., Pisano, C., and Darwiche, N. (2018) Mechanism of action of the atypical retinoid ST1926 in colorectal cancer: DNA damage and DNA polymerase α, Am. J. Cancer Res., 8, 39-55.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was financially supported by the Russian Foundation for Basic Research (projects nos. komfi 17-00-00264, AVM; Bel-a 18-54-00024, AVM), by the Belarusian Republican Foundation for Basic Research (project no. B18R-094, MPS) [chapters on DNA polymerases of the Y-family]; and by the Russian Science Foundation (project no. 18-14-00354, AVM) [chapter on reinitiation of DNA synthesis and PrimPol].

Author information

Authors and Affiliations

  1. Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia

    E. S. Shilkin, E. O. Boldinova, A. D. Stolyarenko & A. V. Makarova

  2. Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 220072, Minsk, Republic of Belarus

    R. I. Goncharova & M. P. Smal

  3. Moscow Institute of Physics and Technology, 141701, Dolgoprudny, Moscow Region, Russia

    R. N. Chuprov-Netochin

Authors
  1. E. S. Shilkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. O. Boldinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. D. Stolyarenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. I. Goncharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. N. Chuprov-Netochin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. P. Smal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. V. Makarova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to M. P. Smal or A. V. Makarova.

Ethics declarations

The authors declare no conflict of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shilkin, E.S., Boldinova, E.O., Stolyarenko, A.D. et al. Translesion DNA Synthesis and Reinitiation of DNA Synthesis in Chemotherapy Resistance. Biochemistry Moscow 85, 869–882 (2020). https://doi.org/10.1134/S0006297920080039

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297920080039

Keywords

Search

Navigation