Back to Search
Start Over
A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis
- Source :
- Scientific Reports, Scientific Reports, 2016, 6, pp.29412. ⟨10.1038/srep29412⟩, Scientific Reports, Nature Publishing Group, 2016, 6, pp.29412. ⟨10.1038/srep29412⟩, Scientific Reports (6), 29412. (2016)
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.
- Subjects :
- 0301 basic medicine
Genome instability
Proteomics
irradiation aux rayons gamma
DNA repair
DNA damage
Cellular detoxification
mammalian-cells
Endogeny
cellule mammaire
CHO Cells
Biology
tumor cell
medicine.disease_cause
Article
Genomic Instability
03 medical and health sciences
Cricetulus
gamma-irradiation
medicine
dna-bas damage
[SDV.BV]Life Sciences [q-bio]/Vegetal Biology
Animals
[SDV.BV] Life Sciences [q-bio]/Vegetal Biology
tumorigénèse
protéomique
cellule cancereuse
Genetics
Mutation
Vegetal Biology
Multidisciplinary
030102 biochemistry & molecular biology
tumorigenesis
proteomics
Mutagenesis
Base excision repair
Cell biology
[SDV.TOX] Life Sciences [q-bio]/Toxicology
Oxidative Stress
030104 developmental biology
[SDV.TOX]Life Sciences [q-bio]/Toxicology
activation
Biologie végétale
DNA Damage
Thymidine
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....bcbf7b591ccda10110533444b1751592