The DOI matches its Crossref record; 180 of the 187 references it cites were found in a registry or an index.
DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis
Abstract
DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O(6)-methylguanine adducts that are converted by mismatch repair into DNA double-strand breaks (DSBs), non-repaired N-methylpurines and abasic sites as well as bulky adducts that block DNA replication leading to DSBs that are also directly induced following ionizing radiation. Transcriptional inhibition may also contribute to apoptosis. Cells are equipped with sensors that detect DNA damage and relay the signal via kinases to executors, who on their turn evoke a process that inhibits cell cycle progression and provokes DNA repair or, if this fails, activate the receptor and/or mitochondrial apoptotic cascade. The main DNA damage recognition factors MRN and the PI3 kinases ATM, ATR and DNA-PK, which phosphorylate a multitude of proteins and thus induce the DNA damage response (DDR), will be discussed as well as the downstream players p53, NF-κB, Akt and survivin. We review data and models describing the signaling from DNA damage to the apoptosis executing machinery and discuss the complex interplay between cell survival and death.
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“Phosphorylation activates these downstream proteins resulting in arrest of cell cycle progression, activation of DNA repair and, in cases of severe damage, apoptotic cell death 22, 34, 35.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [35]
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Cites
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7 of the 187 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Peto, 1984, IARC Sci. Publ., 627
- Roos, 2007, Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O(6)-methylguanine, Oncogene, 26, 186, 10.1038/sj.onc.1209785 · DOI
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Oxidative stress and autophagy: The clash between damage and metabolic needs
Filomeni, G., De Zio, D., & Cecconi, F. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.150 · Cited by 2,195
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189
Self-citationDNA repair mechanisms in dividing and non-dividing cells
Iyama, T., & Wilson, D. M. (2013) · DNA Repair · doi:10.1016/j.dnarep.2013.04.015 · Cited by 697
The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents
Zhou, J., Kang, Y., Chen, L., Wang, H., Liu, J., Zeng, S., & Yu, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00343 · Cited by 481
Modernizing the Nonhomologous End-Joining Repertoire: Alternative and Classical NHEJ Share the Stage
Deriano, L., & Roth, D. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155540 · Cited by 496
Metadata
- Authors
- Roos, W. P., & Kaina, B.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Kaina, Bernd
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 332
- Issue
- 2
- Pages
- 237-248
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2064488040
- Cited by
- 879
- References
- 187
- Citations by year
- 2026: 40 · 2025: 37 · 2024: 52 · 2023: 77 · 2022: 77 · 2021: 76 · 2020: 79 · 2019: 63 · 2018: 89 · 2017: 55 · 2016: 64 · 2015: 67 · 2014: 58 · 2013: 32
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- DNA damage response, apoptosis, DNA lesions, DNA mismatch repair, DNA double-strand breaks, abasic sites, bulky DNA adducts, ionizing radiation, temozolomide, cisplatin, DNA repair, MRN complex, ATM, ATR, DNA-dependent protein kinase, p53, NF-κB, Akt, survivin, transcriptional inhibition, cell cycle arrest, cancer therapy
- MeSH terms
- Survivin, Animals, Antineoplastic Agents, Cell Cycle, DNA, DNA Damage, DNA Repair, Guanine, Humans, Neoplasms, Phosphorylation, Radiation, Ionizing, Signal Transduction, NF-kappa B, Cell Death, Apoptosis, DNA Adducts, Inhibitor of Apoptosis Proteins, Proto-Oncogene Proteins c-akt
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