The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
The pathological response to DNA damage does not contribute to p53-mediated tumour suppression
Abstract
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 injury. 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 pathologies 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 states, 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 p19(ARF)--a tumour suppressor induced not by DNA damage, but by oncogenic disruption of the cell cycle.
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“Although the p53-mediated DNA damage response appears not to be part of p53’s function as tumor suppressor,164 it does support cell viability.”
From Census and evaluation of p53 target genes (2017) · cites this paper as [164]
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Metadata
- Authors
- Christophorou, M. A., Ringshausen, I., Finch, A. J., Swigart, L. B., & Evan, G. I.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Evan, G. I.
- Venue
- Nature
- Published
- 2006-09
- Volume
- 443
- Issue
- 7108
- Pages
- 214-217
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1970249544
- Cited by
- 382
- References
- 30
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3 · 2023: 10 · 2022: 6 · 2021: 13 · 2020: 11 · 2019: 8 · 2018: 5 · 2017: 17 · 2016: 19 · 2015: 19 · 2014: 26 · 2013: 24 · 2012: 23
- FWCI
- 21.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- University of California, San Francisco
- National Institute on Aging
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, tumor suppression, DNA damage response, radiation-induced lymphoma, whole-body irradiation, ARF, oncogene activation, cell cycle arrest, apoptosis, lymphomagenesis
- MeSH terms
- Animals, DNA Damage, Lymphoma, Neoplasms, Radiation-Induced, Tumor Suppressor Protein p53, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Protein p14ARF, Mice
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