DNA repair, genome stability and cancer: a historical perspective

Abstract

The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy.

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Figure 1: Timeline showing the key concepts and findings relating to the role of the DNA damage response in the development of cancer.
Figure 2: How the DNA damage response pathways influence steps leading to cancer.
Figure 3: Many proteins involved in the DNA damage response are mutated in cancer.

References

  1. 1

    Boveri, T. Concerning the origin of malignant tumours by Theodor Boveri. J. Cell Sci. 121 (Suppl. 1), 1–84 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2

    Burdette, W. J. The significance of mutation in relation to the origin of tumors: a review. Cancer Res. 15, 201–226 (1955).

    CAS  PubMed  Google Scholar 

  3. 3

    Muller, H. J. Artificial transmutation of the gene. Science 66, 84–87 (1927).

    Article  CAS  PubMed  Google Scholar 

  4. 4

    Muller, H. J. The production of mutations by X-rays. Proc. Natl Acad. Sci. USA 14, 714–726 (1928).

    Article  CAS  PubMed  Google Scholar 

  5. 5

    Hall, E. J. From chimney sweeps to oncogenes: the quest for the causes of cancer. Radiology 179, 297–306 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. 6

    Pott, P. The first description of an occupational cancer in 1777 (scrotal cancer, cancer of chimney sweeps). Bull. Soc. Liban. Hist. Med. 1993, 98–101 (in French) (1993).

    Google Scholar 

  7. 7

    Waldron, H. A. A brief history of scrotal cancer. Br. J. Ind. Med. 40, 390–401 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8

    Franklin, R. E. & Gosling, R. G. Evidence for 2-chain helix in crystalline structure of sodium deoxyribonucleate. Nature 172, 156–157 (1953).

    Article  CAS  PubMed  Google Scholar 

  9. 9

    Watson, J. D. & Crick, F. H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171, 737–738 (1953).

    Article  CAS  Google Scholar 

  10. 10

    Brookes, P. & Lawley, P. D. The reaction of mustard gas with nucleic acids in vitro and in vivo. Biochem. J. 77, 478–484 (1960).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Brookes, P. & Lawley, P. D. The reaction of mono- and di-functional alkylating agents with nucleic acids. Biochem. J. 80, 496–503 (1961).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Brookes, P. & Lawley, P. D. Evidence for the binding of polynuclear aromatic hydrocarbons to the nucleic acids of mouse skin: relation between carcinogenic power of hydrocarbons and their binding to deoxyribonucleic acid. Nature 202, 781–784 (1964).

    Article  CAS  PubMed  Google Scholar 

  13. 13

    Ames, B. N. A combined bacterial and liver test system for detection and classification of carcinogens as mutagens. Genetics 78, 91–95 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Setlow, R. B. The photochemistry, photobiology, and repair of polynucleotides. Prog. Nucleic Acid. Res. Mol. Biol. 8, 257–295 (1968).

    Article  CAS  PubMed  Google Scholar 

  15. 15

    Pettijohn, D. & Hanawalt, P. Evidence for repair-replication of ultraviolet damaged DNA in bacteria. J. Mol. Biol. 9, 395–410 (1964).

    Article  CAS  PubMed  Google Scholar 

  16. 16

    Friedberg, E. C. & Goldthwait, D. A. Endonuclease II of E. coli. Cold Spring Harb. Symp. Quant. Biol. 33, 271–275 (1968).

    Article  CAS  PubMed  Google Scholar 

  17. 17

    Laval, J. & Laval, F. in Molecular and Cellular Aspects of Carcinogen Screening Tests (eds Montesano, H., Bartsch, L. & Tomatis, L.) 55–73 (IARC Press, 1980).

    Google Scholar 

  18. 18

    Lindahl, T. An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues. Proc. Natl Acad. Sci. USA 71, 3649–3653 (1974).

    Article  CAS  PubMed  Google Scholar 

  19. 19

    Ljungquist, S. & Lindahl, T. A mammalian endonuclease specific for apurinic sites in double-stranded deoxyribonucleic acid. I. Purification and general properties. J. Biol. Chem. 249, 1530–1535 (1974).

    CAS  PubMed  Google Scholar 

  20. 20

    Friedberg, E. C. A brief history of the DNA repair field. Cell Res. 18, 3–7 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. 21

    Laval, F. Repair of methylated bases in mammalian cells during adaptive response to alkylating agents. Biochimie 67, 361–364 (1985).

    Article  CAS  PubMed  Google Scholar 

  22. 22

    Cleaver, J. E. Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc. Natl Acad. Sci. USA 63, 428–435 (1969).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Lehmann, A. R., McGibbon, D. & Stefanini, M. Xeroderma pigmentosum. Orphanet J. Rare Dis. 6, 70 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24

    Leach, F. S. et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75, 1215–1225 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. 25

    Fishel, R. et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75, 1027–1038 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Bronner, C. E. et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368, 258–261 (1994).

    Article  CAS  PubMed  Google Scholar 

  27. 27

    Papadopoulos, N. et al. Mutation of a mutL homolog in hereditary colon cancer. Science 263, 1625–1629 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. 28

    Cui, Z. et al. Association between polymorphisms in XRCC1 gene and clinical outcomes of patients with lung cancer: a meta-analysis. BMC Cancer 12, 71 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Yamtich, J., Nemec, A. A., Keh, A. & Sweasy, J. B. A germline polymorphism of DNA polymerase beta induces genomic instability and cellular transformation. PLoS Genet. 8, e1003052 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Karahalil, B., Bohr, V. A. & Wilson, D. M. Impact of DNA polymorphisms in key DNA base excision repair proteins on cancer risk. Hum. Exp. Toxicol. 31, 981–1005 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Polani, P. E. in Human Genetics: Possibilities and Realities (eds Porter, R. & O'Connor, M.) 81–131 (Excerpta Medica, 1979).

    Google Scholar 

  32. 32

    Moldovan, G. L. & D'Andrea, A. D. How the Fanconi anemia pathway guards the genome. Annu. Rev. Genet. 43, 223–249 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33

    Gray, M. D. et al. The Werner syndrome protein is a DNA helicase. Nat. Genet. 17, 100–103 (1997).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Hartman, A. R. et al. Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer 118, 2787–2795 (2012).

    Article  CAS  PubMed  Google Scholar 

  35. 35

    Cavanagh, H. & Rogers, K. M. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hered. Cancer Clin. Pract. 13, 16 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Banerjee, T. & Brosh, R. M. Jr. RECQL: a new breast cancer susceptibility gene. Cell Cycle https://dx.doi.org/10.1080/15384101.2015.1066539 (2015).

  37. 37

    Lindell, B. & Sowby, D. The 1958 UNSCEAR report. J. Radiol. Prot. 28, 277–282 (2008).

    Article  PubMed  Google Scholar 

  38. 38

    Yang, T. C., Craise, L. M., Mei, M. T. & Tobias, C. A. Neoplastic cell transformation by heavy charged particles. Radiat. Res. Suppl. 8, S177–S187 (1985).

    Article  CAS  PubMed  Google Scholar 

  39. 39

    Taylor, A. M. et al. Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 258, 427–429 (1975).

    Article  CAS  PubMed  Google Scholar 

  40. 40

    Shiloh, Y., Tabor, E. & Becker, Y. Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts. Cancer Res. 42, 2247–2249 (1982).

    CAS  PubMed  Google Scholar 

  41. 41

    Kastan, M. B. et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71, 587–597 (1992).

    Article  CAS  PubMed  Google Scholar 

  42. 42

    Boulton, S. J. et al. Combined functional genomic maps of the C. elegans DNA damage response. Science 295, 127–131 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. 43

    Berenblum, I. & Shubik, P. The role of croton oil applications, associated with a single painting of a carcinogen, in tumour induction of the mouse's skin. Br. J. Cancer 1, 379–382 (1947).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Farber, E. The multistep nature of cancer development. Cancer Res. 44, 4217–4223 (1984).

    CAS  PubMed  Google Scholar 

  45. 45

    Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975).

    CAS  PubMed  Google Scholar 

  46. 46

    Farber, E. Carcinogenesis—cellular evolution as a unifying thread: presidential address. Cancer Res. 33, 2537–2550 (1973).

    CAS  PubMed  Google Scholar 

  47. 47

    Weinberg, R. A. The action of oncogenes in the cytoplasm and nucleus. Science 230, 770–776 (1985).

    Article  CAS  PubMed  Google Scholar 

  48. 48

    Vogelstein, B. & Kinzler, K. W. The multistep nature of cancer. Trends Genet. 9, 138–141 (1993).

    Article  CAS  PubMed  Google Scholar 

  49. 49

    Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50

    Nowell, P. C. The clonal evolution of tumor cell populations. Science 194, 23–28 (1976).

    CAS  Google Scholar 

  51. 51

    Chen, P. L., Chen, Y. M., Bookstein, R. & Lee, W. H. Genetic mechanisms of tumor suppression by the human p53 gene. Science 250, 1576–1580 (1990).

    Article  CAS  PubMed  Google Scholar 

  52. 52

    Loeb, L. A., Springgate, C. F. & Battula, N. Errors in DNA replication as a basis of malignant changes. Cancer Res. 34, 2311–2321 (1974).

    CAS  PubMed  Google Scholar 

  53. 53

    Loeb, L. A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 51, 3075–3079 (1991).

    CAS  Google Scholar 

  54. 54

    Fox, E. J., Prindle, M. J. & Loeb, L. A. Do mutator mutations fuel tumorigenesis? Cancer Metastasis Rev. 32, 353–361 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 55

    Fox, E. J. & Loeb, L. A. Cancer: one cell at a time. Nature 512, 143–144 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56

    Gurdon, J. B. & Uehlinger, V. “Fertile” intestine nuclei. Nature 210, 1240–1241 (1966).

    Article  CAS  PubMed  Google Scholar 

  57. 57

    McKinnell, R. G., Deggins, B. A. & Labat, D. D. Transplantation of pluripotential nuclei from triploid frog tumors. Science 165, 394–396 (1969).

    Article  CAS  Google Scholar 

  58. 58

    Mintz, B. & Illmensee, K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc. Natl Acad. Sci. USA 72, 3585–3589 (1975).

    Article  CAS  Google Scholar 

  59. 59

    Illmensee, K. & Mintz, B. Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts. Proc. Natl Acad. Sci. USA 73, 549–553 (1976).

    Article  CAS  PubMed  Google Scholar 

  60. 60

    Bird, A. P. The relationship of DNA methylation to cancer. Cancer Surv. 28, 87–101 (1996).

    CAS  PubMed  Google Scholar 

  61. 61

    Deuel, T. F., Huang, J. S., Huang, S. S., Stroobant, P. & Waterfield, M. D. Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells. Science 221, 1348–1350 (1983).

    Article  CAS  PubMed  Google Scholar 

  62. 62

    Waterfield, M. D. et al. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304, 35–39 (1983).

    Article  CAS  PubMed  Google Scholar 

  63. 63

    Lees-Miller, S. P. et al. Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0. J. Virol. 70, 7471–7477 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Weitzman, M. D. & Weitzman, J. B. What's the damage? The impact of pathogens on pathways that maintain host genome integrity. Cell Host Microbe 15, 283–294 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Bishop, J. M. Enemies within: the genesis of retrovirus oncogenes. Cell 23, 5–6 (1981).

    Article  CAS  PubMed  Google Scholar 

  66. 66

    Cooper, G. M. Cellular transforming genes. Science 217, 801–806 (1982).

    Article  CAS  PubMed  Google Scholar 

  67. 67

    Denko, N. C., Giaccia, A. J., Stringer, J. R. & Stambrook, P. J. The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. Proc. Natl Acad. Sci. USA 91, 5124–5128 (1994).

    Article  CAS  PubMed  Google Scholar 

  68. 68

    Mai, S., Fluri, M., Siwarski, D. & Huppi, K. Genomic instability in MycER-activated Rat1A-MycER cells. Chromosome Res. 4, 365–371 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. 69

    Felsher, D. W. & Bishop, J. M. Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc. Natl Acad. Sci. USA 96, 3940–3944 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. 70

    Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Zindy, F. et al. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev. 12, 2424–2433 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Vafa, O. et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol. Cell 9, 1031–1044 (2002).

    Article  CAS  Google Scholar 

  73. 73

    Karlsson, A. et al. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression. Proc. Natl Acad. Sci. USA 100, 9974–9979 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. 74

    Lindstrom, M. S. & Wiman, K. G. Myc and E2F1 induce p53 through p14ARF-independent mechanisms in human fibroblasts. Oncogene 22, 4993–5005 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. 75

    Minella, A. C. et al. p53 and p21 form an inducible barrier that protects cells against cyclin E-cdk2 deregulation. Curr. Biol. 12, 1817–1827 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. 76

    Spruck, C. H., Won, K. A. & Reed, S. I. Deregulated cyclin E induces chromosome instability. Nature 401, 297–300 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Ekholm-Reed, S. et al. Deregulation of cyclin E in human cells interferes with prereplication complex assembly. J. Cell Biol. 165, 789–800 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Bartkova, J. et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864–870 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Gorgoulis, V. G. et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907–913 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80

    Wahl, G. M. & Carr, A. M. The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat. Cell Biol. 3, E277–E286 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Baker, S. J. et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244, 217–221 (1989).

    Article  CAS  Google Scholar 

  82. 82

    Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J. & Cleveland, J. L. Disruption of the ARF–Mdm2–p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev. 13, 2658–2669 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Lee, H. et al. Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2. Mol. Cell 4, 1–10 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. 84

    Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 319, 1352–1355 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Martincorena, I. et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880–886 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Lindahl, T. The Croonian Lecture, 1996: endogenous damage to DNA. Phil. Trans. R. Soc. Lond. B 351, 1529–1538 (1996).

    Article  CAS  Google Scholar 

  87. 87

    Pearl, L. H., Schierz, A. C., Ward, S. E., Al-Lazikani, B. & Pearl, F. M. Therapeutic opportunities within the DNA damage response. Nat. Rev. Cancer 15, 166–180 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 88

    Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011).

  89. 89

    Lord, C. J., Tutt, A. N. & Ashworth, A. Synthetic lethality and cancer therapy: lessons learned from the development of PARP inhibitors. Annu. Rev. Med. 66, 455–470 (2015).

    Article  CAS  Google Scholar 

  90. 90

    Lord, C. J. & Ashworth, A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat. Med. 19, 1381–1388 (2013).

    Article  CAS  Google Scholar 

  91. 91

    Callen, E. et al. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153, 1266–1280 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. 92

    Bouwman, P. et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17, 688–695 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 93

    Schoppy, D. W. et al. Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. J. Clin. Invest. 122, 241–252 (2012).

    Article  CAS  PubMed  Google Scholar 

  94. 94

    Hill, R. F. A radiation-sensitive mutant of Escherichia coli. Biochim. Biophys. Acta 30, 636–637 (1958).

    Article  CAS  PubMed  Google Scholar 

  95. 95

    Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Murphree, A. L. & Benedict, W. F. Retinoblastoma: clues to human oncogenesis. Science 223, 1028–1033 (1984).

    Article  CAS  PubMed  Google Scholar 

  97. 97

    Hartwell, L. H. & Weinert, T. A. Checkpoints: controls that ensure the order of cell cycle events. Science 246, 629–634 (1989).

    Article  CAS  PubMed  Google Scholar 

  98. 98

    Kinzler, K. W. & Vogelstein, B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 386, 761–763 (1997).

    Article  CAS  PubMed  Google Scholar 

  99. 99

    Moynahan, M. E., Chiu, J. W., Koller, B. H. & Jasin, M. Brca1 controls homology-directed DNA repair. Mol. Cell 4, 511–518 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. 100

    Sharan, S. K. et al. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386, 804–810 (1997).

    Article  CAS  PubMed  Google Scholar 

  101. 101

    Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    Article  CAS  Google Scholar 

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Acknowledgements

A.M.C. is funded by the Medical Research Council (grant G1100074). L.H.P. is supported by the Cancer Research UK Programme grant C302/A14532, and P.A.J. is supported by the EU Seventh Framework Programme (FP7) RISK – IR project under grant agreement no. 323267. The authors also thank F. Pearl for useful discussions.

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Correspondence to Penny A. Jeggo or Laurence H. Pearl or Antony M. Carr.

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Jeggo, P., Pearl, L. & Carr, A. DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer 16, 35–42 (2016). https://doi.org/10.1038/nrc.2015.4

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