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The evolution of diverse biological responses to DNA damage: insights from yeast and p53

Nature Cell Biology volume 3, pages E277–E286 (2001)Cite this article

An Erratum to this article was published on 01 April 2002

Abstract

The cellular response to ionizing radiation provides a conceptual framework for understanding how a yeast checkpoint system, designed to make binary decisions between arrest and cycling, evolved in a way as to allow reversible arrest, senescence or apoptosis in mammals. We propose that the diversity of responses to ionizing radiation in mammalian cells is possible because of the addition of a new regulatory control module involving the tumour-suppressor gene p53. We review the complex mechanisms controlling p53 activity and discuss how the p53 regulatory module enables cells to grow, arrest or die by integrating DNA damage checkpoint signals with the response to normal mitogenic signalling and the aberrant signalling engendered by oncogene activation.

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Figure 1: A schematic representation of the checkpoint pathways in a, yeast, b, Drosophila and c, mammalian cells.
Figure 2: Abbreviated diagram of p53 structural domains, modification sites and coregulators.
Figure 3: Mechanisms for p53 activation by activated oncogenes.

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Acknowledgements

The authors apologize to our many colleagues whose seminal work was not referenced owing to space constraints. We thank our colleagues M. Hubanks, P. Jeggo, M. Oren, M. Wade, J. Stommel, and F. Toledo for many helpful suggestions regarding the manuscript. G.M.W. was funded by grants from the National Cancer Institute, Cancer Research Program (California), Bosch Foundation and National Institutes of Health. A.M.C. was funded by grants from the Medical Research Council and the Human Frontiers Science Program.

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  1. Gene Expression Laboratory, The Salk Institute, La Jolla, 92037, California, USA

    Geoffrey M. Wahl

  2. Genome Damage and Stability Centre, University of Sussex, Falmer, BN1 9RR, Brighton, UK

    Antony M. Carr

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Wahl, G., Carr, A. The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol 3, E277–E286 (2001). https://doi.org/10.1038/ncb1201-e277

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