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The impact of a negligent G2/M checkpoint on genomic instability and cancer induction

Nature Reviews Cancer volume 7, pages 861–869 (2007)Cite this article

Abstract

DNA damage responses (DDR) encompass DNA repair and signal transduction pathways that effect cell cycle checkpoint arrest and/or apoptosis. How DDR pathways respond to low levels of DNA damage, including low doses of ionizing radiation, is crucial for assessing environmental cancer risk. It has been assumed that damage-induced cell cycle checkpoints respond to a single double strand break (DSB) but the G2/M checkpoint, which prevents entry into mitosis, has recently been shown to have a defined threshold of 10–20 DSBs. Here, we consider the impact of a negligent G2/M checkpoint on genomic stability and cancer risk.

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Figure 1: An overview of mammalian signal transduction pathways activating cell cycle checkpoint arrest after IR.
Figure 2: An overview of DSB repair pathways responding to IR damage.
Figure 3: Encounters with IR exposures and risk estimation.
Figure 4: Impact of a G2/M checkpoint threshold on checkpoint duration and chromosome breakage.
Figure 5: Model for the impact of G2 repair and the G2/M checkpoint on survival and the prevention of chromosome breakage.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Stanbridge, E. J. & Nowell, P. C. Origins of human cancer revisited. Cell 63, 867–874 (1990).

    Article  CAS  PubMed  Google Scholar 

  3. Loeb, L. A. Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res. 54, 5059–5063 (1994).

    CAS  PubMed  Google Scholar 

  4. 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  Google Scholar 

  5. 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  Google Scholar 

  6. Melo, J. V. & Barnes, D. J. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nature Rev. Cancer 7, 441–453 (2007).

    Article  CAS  Google Scholar 

  7. Kops, G. J., Weaver, B. A. & Cleveland, D. W. On the road to cancer: aneuploidy and the mitotic checkpoint. Nature Rev. Cancer 5, 773–785 (2005).

    Article  CAS  Google Scholar 

  8. Mitelman, F., Johansson, B. & Mertens, F. The impact of translocations and gene fusions on cancer causation. Nature Rev. Cancer 7, 233–245 (2007).

    Article  CAS  Google Scholar 

  9. Nijnik, A. et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447, 686–690 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Gellert, M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu. Rev. Biochem. 71, 101–132 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Goodhead, D. T. Initial events in the cellular effects of ionising radiations: clustered damage in DNA. Int. J. Radiat. Biol. 65, 7–17 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Thacker, J. in Advances in Radiation Biology 16, (eds Lett, J. T. & Sinclair, W. K.) 77–124 (Academic Press, San Diego, 1992).

    Google Scholar 

  13. Collins, A. R. Mutant rodent cell lines sensitive to ultraviolet light, ionising radiation and cross-linking agents: a comprehensive survey of genetic and biochemical characteristics. Mutat. Research 293, 99–118 (1993).

    Article  CAS  Google Scholar 

  14. Jeggo, P. A. in Molecular mechanisms in radiation mutagenesis and carcinogenesis (eds Chadwick, K. H., Cox, R., Leenhouts, H. P. & Thacker, J.) 17–22 (European Commission, Luxembourg, 1994).

    Google Scholar 

  15. Wood, R. D., Mitchell, M., Sgouros, J. & Lindahl, T. Human DNA repair genes. Science 291, 1284–1289 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Wood, R. D., Mitchell, M. & Lindahl, T. Human DNA repair genes, 2005. Mutat. Research 577, 275–283 (2005).

    Article  CAS  Google Scholar 

  17. Kurz, E. U. & Lees-Miller, S. P. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst.) 3, 889–900 (2004).

    Article  CAS  Google Scholar 

  18. Abraham, R. T. PI 3-kinase related kinases: 'big' players in stress-induced signaling pathways. DNA Repair (Amst.) 3, 883–887 (2004).

    Article  CAS  Google Scholar 

  19. Shiloh, Y. ATM and related protein kinases: safeguarding genome integrity. Nature Rev. Cancer 3, 155–168 (2003).

    Article  CAS  Google Scholar 

  20. Hartwell, L. H. & Kastan, M. B. Cell cycle control and cancer. Science 266, 1821–1828 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Zhou, B. B. & Elledge, S. J. The DNA damage response: putting checkpoints in perspective. Nature 408, 433–439 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Canman, C. E. et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281, 1677–1679 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Lukas, J., Lukas, C. & Bartek, J. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair (Amst.) 3, 997–1007 (2004).

    Article  CAS  Google Scholar 

  24. Terzoudi, G. I., Manola, K. N., Pantelias, G. E. & Iliakis, G. Checkpoint abrogation in G2 compromises repair of chromosomal breaks in ataxia telangiectasia cells. Cancer Res. 65, 11292–11296 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. O'Driscoll, M. & Jeggo, P. A. The role of double-strand break repair - insights from human genetics. Nature Rev. Genet. 7, 45–54 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Sax, K. Chromosome aberrations induced by X-rays. Genetics 23, 494–516 (1938).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lea, D. E. & Coulson, C. A. The distribution of numbers of mutants in bacterial populations. J. Genetics 49, 264–285 (1949).

    Article  CAS  Google Scholar 

  28. Cornforth, M. N. & Bedford, J. S. in Advances in Radiation Biology (eds Lett, J. T. & Sinclair, W. K.) 17, 423–496 (Academic Press, San Diego, 1993).

    Google Scholar 

  29. Toczyski, D. P., Galgoczy, D. J. & Hartwell, L. H. CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90, 1097–1106 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Harrison, J. C. & Haber, J. E. Surviving the breakup: the DNA damage checkpoint. Annu. Rev. Genet. 40, 209–235 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Bennett, C. B., Snipe, J. R. & Resnick, M. A. A persistent double-strand break destabilizes human DNA in yeast and can lead to G2 arrest and lethality. Cancer Res. 57, 1970–1980 (1997).

    CAS  PubMed  Google Scholar 

  32. Garvik, B., Carson, M. & Hartwell, L. Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol. Cell. Biol. 15, 6128–6138 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Deckbar, D. et al. Chromosome breakage after G2 checkpoint release. J. Cell Biol. 176, 748–755 (2007).

    Article  CAS  Google Scholar 

  34. Riballo, E. et al. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol. Cell 16, 715–724 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Syljuasen, R. G., Jensen, S., Bartek, J. & Lukas, J. Adaptation to the ionizing radiation-induced G2 checkpoint occurs in human cells and depends on checkpoint kinase 1 and Polo-like kinase 1 kinases. Cancer Res. 66, 10253–10257 (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Bartek, J. & Lukas, J. DNA damage checkpoints: from initiation to recovery or adaptation. Curr. Opin. Cell Biol. 19, 238–245 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Yoo, H. Y., Kumagai, A., Shevchenko, A. & Dunphy, W. G. Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Cell 117, 575–588 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Joiner, M. C., Marples, B., Lambin, P., Short, S. C. & Turesson, I. Low-dose hypersensitivity: current status and possible mechanisms. Int. J. Radiat. Oncol. Biol. Phys. 49, 379–389 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Marples, B., Wouters, B. G., Collis, S. J., Chalmers, A. J. & Joiner, M. C. Low-dose hyper-radiosensitivity: a consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. Radiat. Res. 161, 247–255 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Short, S. C., Woodcock, M., Marples, B. & Joiner, M. C. Effects of cell cycle phase on low-dose hyper-radiosensitivity. Int. J. Radiat. Biol. 79, 99–105 (2003).

    Article  CAS  PubMed  Google Scholar 

  41. Taylor, A. M. R. Aataxia telangiectasia genes and predisposition to leukaemia, lymphoma and breast cancer. Brit. J. Cancer 66, 5–9 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kuhne, M. et al. A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res. 64, 500–508 (2004).

    Article  PubMed  Google Scholar 

  43. Cornforth, M. N. & Bedford, J. S. On the nature of a defect in cells from individuals with ataxia-telangiectasia. Science 227, 1589–1591 (1985).

    Article  CAS  PubMed  Google Scholar 

  44. Pandita, T. K. & Hittelman, W. N. The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia-telangiectasia. Radiat. Res. 131, 214–223 (1992).

    Article  CAS  PubMed  Google Scholar 

  45. Jeggo, P. A., Carr, A. M. & Lehmann, A. R. Splitting the ATM: distinct repair and checkpoint defects in ataxia-telangiectasia. Trends Genet. 14, 312–316 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Stiff, T. et al. ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J. 25, 5775–5782 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu, Q. et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14, 1448–1459 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wykes, S. M., Piasentin, E., Joiner, M. C., Wilson, G. D. & Marples, B. Low-dose hyper-radiosensitivity is not caused by a failure to recognize DNA double-strand breaks. Radiat. Res. 165, 516–524 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. 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 

  50. Varon, R. et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93, 467–476 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. Carney, J. P. et al. The hMre11/hRad50 protein complex and Nijmegen breakage-syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93, 477–486 (1998).

    Article  CAS  PubMed  Google Scholar 

  52. Berkovich, E., Monnat, R. J. Jr., & Kastan, M. B. Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nature Cell. Biol. 9, 683–690 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Gudmundsdottir, K. & Ashworth, A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 25, 5864–5874 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Rooney, S. et al. Artemis and p53 cooperate to suppress oncogenic N-myc amplification in progenitor B cells. Proc. Natl Acad. Sci. USA 101, 2410–2415 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gao, Y. et al. Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development. Nature 404, 897–900 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Lim, D. S. et al. Analysis of ku80-mutant mice and cells with deficient levels of p53. Mol. Cell. Biol. 20, 3772–3780 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Linke, S. P., Clarkin, K. C. & Wahl, G. M. p53 mediates permanent arrest over multiple cell cycles in response to gamma-irradiation. Cancer Res. 57, 1171–1179 (1997).

    CAS  PubMed  Google Scholar 

  58. Huang, L. C., Clarkin, K. C. & Wahl, G. M. Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc. Natl Acad. Sci USA 93, 4827–4832 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bartek, J. & Lukas, J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr. Opin. Cell. Biol. 13, 738–747 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. d'Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Xu, B., Kim, S. T., Lim, D. S. & Kastan, M. B. Two molecularly distinct G(2)/M checkpoints are induced by ionizing irradiation. Mol. Cell. Biol. 22, 1049–1059 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wang, X., Khadpe, J., Hu, B., Iliakis, G. & Wang, Y. An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells. J. Biol. Chem. 278, 30869–30874 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Krempler, A., Deckbar, D., Jeggo, P. A. & Lobrich, M. An Imperfect G(2)/M Checkpoint Contributes to Chromosome Instability Following Irradiation of S and G(2) Phase Cells. Cell Cycle 6, 1682–1686 (2007).

    Article  CAS  PubMed  Google Scholar 

  64. Jazayeri, A. et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nature Cell. Biol. 8, 37–45 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Chun, H. H. & Gatti, R. A. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst.) 3, 1187–1196 (2004).

    Article  CAS  Google Scholar 

  66. Moshous, D. et al. Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis. J. Clin. Invest. 111, 381–387 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Buck, D. et al. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV. Eur. J. Immunol. 36, 224–235 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Shivji, M. K. & Venkitaraman, A. R. DNA recombination, chromosomal stability and carcinogenesis: insights into the role of BRCA2. DNA Repair (Amst.) 3, 835–843 (2004).

    Article  CAS  Google Scholar 

  69. Risinger, M. A. & Groden, J. Crosslinks and crosstalk: human cancer syndromes and DNA repair defects. Cancer Cell 6, 539–545 (2004).

    CAS  PubMed  Google Scholar 

  70. Uziel, T. et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 22, 5612–5621 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zou, L. & Elledge, S. J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300, 1542–1548 (2003).

    Article  CAS  PubMed  Google Scholar 

  72. Zou, L., Liu, D. & Elledge, S. J. Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc. Natl Acad. Sci. USA 100, 13827–13832 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mailand, N. et al. Rapid destruction of human Cdc25A in response to DNA damage. Science 288, 1425–1429 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Costanzo, V. et al. Reconstitution of an ATM-dependent checkpoint that inhibits chromosomal DNA replication following DNA damage. Mol. Cell 6, 649–659 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Kuerbitz, S. J., Plunkett, B. S., Walsh, W. V. & Kastan, M. B. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl Acad. Sci. USA 89, 7491–7495 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kastan, M. B. & Bartek, J. Cell-cycle checkpoints and cancer. Nature 432, 316–323 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Taylor, W. R. & Stark, G. R. Regulation of the G2/M transition by p53. Oncogene 20, 1803–1815 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. El-Deiry, W. S. et al. WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825 (1993).

    Article  CAS  PubMed  Google Scholar 

  79. Wang, X. W. et al. GADD45 induction of a G2/M cell cycle checkpoint. Proc. Natl Acad. Sci. USA 96, 3706–3711 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hermeking, H. et al. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol. Cell 1, 3–11 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Hefferin, M. L. & Tomkinson, A. E. Mechanism of DNA double-strand break repair by non-homologous end joining. DNA Repair (Amst.) 4, 639–648 (2005).

    Article  CAS  Google Scholar 

  82. Jeggo, P. A. & Lobrich, M. Radiation induced DNA damage responses. Rad. Prot. Dosim. 122, 124–127 (2006).

    Article  CAS  Google Scholar 

  83. Kruger, I., Rothkamm, K. & Lobrich, M. Enhanced fidelity for rejoining radiation-induced DNA double-strand breaks in the G2 phase of Chinese hamster ovary cells. Nucleic Acids Res. 32, 2677–2684 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Wyman, C. & Kanaar, R. DNA double-strand break repair: all's well that ends well. Annu. Rev. Genet. 40, 363–383 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Rothkamm, K., Kruger, I., Thompson, L. H. & Lobrich, M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol. Cell. Biol. 23, 5706–5715 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Saleh-Gohari, N. et al. Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks. Mol. Cell. Biol. 25, 7158–7169 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. O'Driscoll, M. et al. DNA Ligase IV mutations identified in patients exhibiting development delay and immunodeficiency. Mol. Cell 8, 1175–1185 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Lobrich, M. & Jeggo, P. A. Harmonising the response to DSBs: a new string in the ATM bow. DNA Repair (Amst.) 4, 749–759 (2005).

    Article  CAS  Google Scholar 

  89. Wang, J. et al. Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression. DNA Repair (Amst.) 4, 556–570 (2005).

    Article  CAS  Google Scholar 

  90. Darroudi, F. et al. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle. Mutat. Res. 615, 111–124 (2007).

    Article  CAS  PubMed  Google Scholar 

  91. West, S. C. Molecular views of recombination proteins and their control. Nature Rev. Mol. Cell. Biol. 4, 435–445 (2003).

    Article  CAS  Google Scholar 

  92. UNSCEAR. 565–571 (United Nations, New York, 1988).

  93. Brenner, D. J. et al. Cancer risks attribuw to low doses of ionizing radiation: assessing what we really know. Proc. Natl Acad. Sci. USA 100, 13761–13766 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cardis, E. et al. The 15-country collaborative study of cancer risk among radiation workers in the nuclear industry: estimates of radiation-related cancer risks. Radiat. Res. 167, 396–416 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Preston, D. L., Shimizu, Y., Pierce, D. A., Suyama, A. & Mabuchi, K. Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950–1997. Radiat. Res. 160, 381–407 (2003).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Professor Dudley Goodhead for critically reading the manuscript. The M.L. laboratory is supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung via the Forschungszentrum Karlsruhe, the Deutsche Zentrum für Luft und Raumfahrt e.V., and the Wilhelm Sander-Stiftung. The P.A.J. laboratory is supported by the Medical Research Council, the Department of Health, The Association for International Cancer Research, the Leukaemia Research Fund and EU grant DNA Repair (CT-2005-512,113). Both laboratories are supported by EU grant FI6R-CT-2003-508,842 (RiscRad).

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  1. Penny A. Jeggo is at the Genome Damage and Stability Centre, University of Sussex, East Sussex, BN1 9RQ, UK.

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  1. Markus Löbrich is at the Darmstadt University of Technology, Radiation Biology and DNA Repair, 64287 Darmstadt, Germany.,

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Löbrich, M., Jeggo, P. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer 7, 861–869 (2007). https://doi.org/10.1038/nrc2248

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