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Cell-cycle checkpoints and cancer

Abstract

All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation. Highly conserved DNA-repair and cell-cycle checkpoint pathways allow cells to deal with both endogenous and exogenous sources of DNA damage. How much an individual is exposed to these agents and how their cells respond to DNA damage are critical determinants of whether that individual will develop cancer. These cellular responses are also important for determining toxicities and responses to current cancer therapies, most of which target the DNA.

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Figure 1: General scheme of responses to DNA damage or replication-fork arrest and the impact on cell fate, genomic instability and cancer development.
Figure 2: Scheme of mechanisms that lead to the induction of ATM- and ATR-directed cellular activities.
Figure 3: A simplified scheme of cell-cycle checkpoint pathways induced in response to DNA damage (here DSBs), with highlighted tumour suppressors shown in red and proto-oncogenes shown in green.
Figure 4: Schematic representation of two main steps that contribute to a spectrum of mutations leading to cancer development.

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Acknowledgements

We thank members of our laboratories for invaluable discussions, and apologize to colleagues whose work could only be cited indirectly. The authors are supported by the American Lebanese Syrian Associated Charities (ALSAC) of the St. Jude Children's Research Hospital and by grants from the NIH (M.B.K.), the Danish Cancer Society and the European Union (J.B.).

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Kastan, M., Bartek, J. Cell-cycle checkpoints and cancer. Nature 432, 316–323 (2004). https://doi.org/10.1038/nature03097

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