Access

Letter

Nature 443, 214-217 (14 September 2006) | doi:10.1038/nature05077; Received 1 May 2006; Accepted 13 July 2006; Published online 6 September 2006

Open Innovation Challenges

naturejobs

The pathological response to DNA damage does not contribute to p53-mediated tumour suppression

M. A. Christophorou1, I. Ringshausen1, A. J. Finch1, L. Brown Swigart1 & G. I. Evan1

  1. Cancer Research Institute and Department of Cellular & Molecular Pharmacology, Comprehensive Cancer Center, University of California, San Francisco, California 94143, USA

Correspondence to: G. I. Evan1 Correspondence and requests for materials should be addressed to G.I.E. (Email: gevan@cc.ucsf.edu).

Top

The p53 protein has a highly evolutionarily conserved role in metazoans as 'guardian of the genome', mediating cell-cycle arrest and apoptosis in response to genotoxic injury1. In large, long-lived animals with substantial somatic regenerative capacity, such as vertebrates, p53 is an important tumour suppressor—an attribute thought to stem directly from its induction of death or arrest in mutant cells with damaged or unstable genomes. Chemotherapy and radiation exposure both induce widespread p53-dependent DNA damage. This triggers potentially lethal pathologies2 that are generally deemed an unfortunate but unavoidable consequence of the role p53 has in tumour suppression. Here we show, using a mouse model in which p53 status can be reversibly switched in vivo between functional and inactive states3, that the p53-mediated pathological response to whole-body irradiation, a prototypical genotoxic carcinogen, is irrelevant for suppression of radiation-induced lymphoma. In contrast, delaying the restoration of p53 function until the acute radiation response has subsided abrogates all of the radiation-induced pathology yet preserves much of the protection from lymphoma. Such protection is absolutely dependent on p19ARF—a tumour suppressor induced not by DNA damage, but by oncogenic disruption of the cell cycle.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Cancer biology Can less be more for p53?

Nature News and Views (14 Sep 2006)