Cited by 382Cancer-related Molecular PathwaysDNA Repair MechanismsCell death mechanisms and regulation

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

Christophorou, M. A., Ringshausen, I., Finch, A. J., Swigart, L. Brown, Evan, G. I.·2006·Nature

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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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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.
ORCID: Christophorou, M. A.
Ringshausen, I.
Finch, A. J.
Swigart, L. Brown
Evan, G. I.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-09
Volume: 443
Issue: 7108
Pages: 214-217
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature05077
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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks