Defying death after DNA damage
Abstract
DNA damage frequently triggers death by apoptosis. The irreversible decision to die can be facilitated or forestalled through integration of a wide variety of stimuli from within and around the cell. Here we address some fundamental questions that arise from this model. Why should DNA damage initiate apoptosis in the first place? In damaged cells, what are the alternatives to death and why should they be selected in some circumstances but not others? What signals register DNA damage and how do they impinge on the effector pathways of apoptosis? Is there a suborganellar apoptosome complex effecting the integration of death signals within the nucleus, just as there is in the cytoplasm? And what are the consequences of failure to initiate apoptosis in response to DNA damage?
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In metazoans, a single double-strand break has the potential to be lethal if it remains unrepaired.
“In metazoans, a singular DSB has the potential to be lethal if it remains unrepaired [32].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [32]
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“In metazoans, a singular DSB has the potential to be lethal if it remains unre-paired [32].”
Background
- Authors
- Rich, T., Allen, R. L., & Wyllie, A. H.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Wyllie, Andrew H.
- ORCID
- Allen, Rachel L.
- Venue
- Nature
- Published
- 2000-10
- Volume
- 407
- Issue
- 6805
- Pages
- 777-783
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1656708631
- Cited by
- 724
- References
- 6
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 16 · 2022: 13 · 2021: 10 · 2020: 13 · 2019: 10 · 2018: 21 · 2017: 20 · 2016: 18 · 2015: 31 · 2014: 24 · 2013: 26 · 2012: 27
- FWCI
- 3.92
- 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)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- DNA damage, apoptosis, cell death, DNA damage signaling, apoptosome
- MeSH terms
- Animals, Carrier Proteins, DNA Damage, DNA-Binding Proteins, Forecasting, Humans, Transcription Factors, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-abl, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Tumor Suppressor Proteins, Transcription Factor DP1, E2F Transcription Factors, Retinoblastoma-Binding Protein 1, Ataxia Telangiectasia Mutated Proteins
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