ArticleThe Journal of biological chemistry2013
Chromatin collapse during caspase-dependent apoptotic cell death requires DNA fragmentation factor, 40-kDa subunit-/caspase-activated deoxyribonuclease-mediated 3'-OH single-strand DNA breaks.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Electrostatic control of chromatin compaction safeguards against apoptotic DNA release.The EMBO journal · 2026Article
- How cells die determines the consequences of tissue repair: roles of programmed cell death in lung injury on the progression of pulmonary fibrosis.Molecular and cellular biochemistry · 2026Review
- Knockdown of caspase-activated DNase and B-cell lymphoma 2 inhibits cell proliferation and drug resistance in TP53-mutant multiple myeloma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- DNA fragmentation factor B suppresses interferon to enable cancer persister cell regrowth.Nature cell biology · 2025Article
- Targeting Cancer Cell Fate: Apoptosis, Autophagy, and Gold Nanoparticles in Treatment Strategies.Current issues in molecular biology · 2025Review
- Kinetic Effects of Transferrin-Conjugated Gold Nanoparticles on the Antioxidant Glutathione-Thioredoxin Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA.Genome medicine · 2022Article
- Cannabidiol and Cannabigerol Inhibit Cholangiocarcinoma Growth In Vitro via Divergent Cell Death Pathways.Biomolecules · 2022Article
- Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells.Cancers · 2021Article
- Ketoprofen Combined with UVA Irradiation Exerts Higher Selectivity in the Mode of Action against Melanotic Melanoma Cells than against Normal Human Melanocytes.International journal of molecular sciences · 2021Article
- Zerumbone mediates apoptosis and induces secretion of proinflammatory cytokines in breast carcinoma cell culture.Iranian journal of basic medical sciences · 2021Article
- The role of the DFF40/CAD endonuclease in genomic stability.Apoptosis : an international journal on programmed cell death · 2021Review
- Acetylcholinesterase promotes apoptosis in insect neurons.Apoptosis : an international journal on programmed cell death · 2020Article
- Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells.Nature communications · 2019Article
- PRAK Is Required for the Formation of Neutrophil Extracellular Traps.Frontiers in immunology · 2019Article
- Extracellular DNA and autoimmune diseases.Cellular & molecular immunology · 2018Review
- Bufalin induced apoptosis in SCC‑4 human tongue cancer cells by decreasing Bcl‑2 and increasing Bax expression via the mitochondria‑dependent pathway.Molecular medicine reports · 2017Article
- Review on the Potential Therapeutic Roles ofJournal of pharmacopuncture · 2017Review
- Investigating right ovary degeneration in chick embryos by transcriptome sequencing.The Journal of reproduction and development · 2017Article
- An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptotic nuclear morphology and oligonucleosomal double-strand DNA fragments (also known as DNA ladder) are considered the hallmarks of apoptotic cell death. From a classic point of view, these two processes occur concomitantly. Once activated, DNA fragmentation factor, 40-kDa subunit (DFF40)/caspase-activated DNase (CAD) endonuclease hydrolyzes the DNA into oligonucleosomal-size pieces, facilitating the chromatin package. However, the dogma that the apoptotic nuclear morphology depends on DNA fragmentation has been questioned. Here, we use different cellular models, including MEF CAD(-/-) cells, to unravel the mechanism by which DFF40/CAD influences chromatin condensation and nuclear collapse during apoptosis. Upon apoptotic insult, SK-N-AS cells display caspase-dependent apoptotic nuclear alterations in the absence of internucleosomal DNA degradation. The overexpression of a wild-type form of DFF40/CAD endonuclease, but not of different catalytic-null mutants, restores the cellular ability to degrade the chromatin into oligonucleosomal-length fragments. We show that apoptotic nuclear collapse requires a 3'-OH endonucleolytic activity even though the internucleosomal DNA degradation is impaired. Moreover, alkaline unwinding electrophoresis and In Situ End-Labeling (ISEL)/In Situ Nick Translation (ISNT) assays reveal that the apoptotic DNA damage observed in the DNA ladder-deficient SK-N-AS cells is characterized by the presence of single-strand nicks/breaks. Apoptotic single-strand breaks can be impaired by DFF40/CAD knockdown, abrogating nuclear collapse and disassembly. In conclusion, the highest order of chromatin compaction observed in the later steps of caspase-dependent apoptosis relies on DFF40/CAD-mediated DNA damage by generating 3'-OH ends in single-strand rather than double-strand DNA nicks/breaks.
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