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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.

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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, 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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