Unrepaired oxidative DNA damage induces an ATR/ATM apoptotic-like response in quiescent fission yeast
Open accessAbstract
Programmed cell death is a term which refers to a genetic decision of self-killing or suicide of a cell. Programmed cell death is not restricted to multicellular organisms and was described in a wide range of unicellular eukaryotes, indicating phylogenetically conserved functions, that participate in an adaptive response to cellular stress. Here we review and discuss our observations recently published in the EMBO Journal,(1) that non-dividing fission yeast, Schizosaccharomyces pombe, exhibits a DNA damage response leading to cell death. We found that Tdp1 protects quiescent S. pombe cells against oxidative DNA damage. Tdp1 is a well-conserved tyrosyl-DNA phosphodiesterase required for single-strand break DNA repair, the mutation of Tdp1 is responsible for the recessively inherited syndrome spinocerebellar ataxia with axonal neuropathy (SCAN1) in humans. We found that tdp1 mutant yeast cells grow, as well as the wild-type cells, during the vegetative state, but progressively die in the quiescent state. We showed that, in the absence of Tdp1, the accumulation of unrepaired oxidative DNA damage triggers a genetic response, leading to checkpoint-dependent (ATM/ATR) nuclear DNA degradation, reminiscent of apoptosis. Our results indicate that the reactive oxygen species (ROS) produced during mitochondrial respiration are the main DNA damaging agents in the physiological quiescent state.
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When TDP1 is absent, unrepaired oxidative DNA damage causes an apoptotic-like response that depends on ATR/ATM.
“In the absence of TDP1, unrepaired oxidative DNA damage triggers an ATR/ATM-dependent apoptotic-like response.”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [198]
Reactive oxygen species under normal quiescent conditions pose a harmful threat to genomic stability.
“This infers that ROS under physiological quiescent conditions represent a detrimental threat to genomic stability [198].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [198]
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Yan, S., Sorrell, M., & Berman, Z. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1666-4 · Cited by 247 · see citing works
- Authors
- Arcangioli, B., & Ben Hassine, S.
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2009-08
- Volume
- 8
- Issue
- 15
- Pages
- 2326-2331
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2094943390
- Cited by
- 10
- References
- 0
- Citations by year
- 2025: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2012: 2
- FWCI
- 0.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-06-BLAN-0271)
- China Scholarship Council
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- oxidative DNA damage, programmed cell death, Schizosaccharomyces pombe, TDP1, tyrosyl-DNA phosphodiesterase, ATM, ATR, DNA damage response, quiescent cells, reactive oxygen species, mitochondrial respiration, nuclear DNA degradation
- MeSH terms
- DNA Damage, DNA Repair, DNA-Binding Proteins, Oxidation-Reduction, Phosphoric Diester Hydrolases, Protein Kinases, Schizosaccharomyces, Cell Death, Apoptosis, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Cell Cycle Proteins, Tumor Suppressor Proteins, Schizosaccharomyces pombe Proteins, DNA Breaks, Single-Stranded, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2
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