ArticleCurrent biology : CB2021
Nuclear Deformation Causes DNA Damage by Increasing Replication Stress.
Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
138 citing papers in PubMed, 203 citations in OpenAlex.
- Nuclear mechanobiology in confined cell migration.Nucleus (Austin, Tex.) · 2026Review
- Nuclear mechanobiology: a brief history and five unresolved questions.Nucleus (Austin, Tex.) · 2026Article
- Nuclear envelope rupture and resealing: mechanisms, consequences, and disease implications.Biochemical Society transactions · 2026Review
- Atypical fusion among non-malignant cells: Unveiling the link between post-fusion-induced genome chaos and cancer initiation.Cancer cell international · 2026Article
- In vivo DNA damage protection during cell migration across confining embryonic tissue environments.Nature cell biology · 2026Article
- Article
- Mechanical regulation of cell memory.Nature structural & molecular biology · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Neuro-Mechanical Regulation of Vascular Smooth Muscle Cell Behaviour Under Ageing-Associated Substrate Stiffness.Current issues in molecular biology · 2026Article
- Article
- Dual and opposing roles of the EXD2 exonuclease in the resolution of RNA-DNA hybrids.Nucleic acids research · 2026Article
- Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton.Nature materials · 2026Article
- Unraveling the link between genomic instability and tumor immune evasion in oral squamous cell carcinoma: Role of CBMN assay and emerging perspectives.Medical oncology (Northwood, London, England) · 2026Review
- Changes in nuclear and actin mechanics from G1 to G2 affect nuclear integrity.Journal of cell science · 2026Article
- Article
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Assessment of DNA Variations From Two In Vivo Skeletal Muscle Disorder Mouse Models Using Complementary Square-Wave Voltammetry and LC-MS/MS Analysis.Chembiochem : a European journal of chemical biology · 2026Article
- Mechanomedicine-guided mechanical preconditioning of dental-derived stromal cells for tissue regeneration.Stem cell research & therapy · 2026Review
- The nuclear structural protein NuMA is required for efficient DNA replication by ensuring association of core replication factors to replication forks.bioRxiv : the preprint server for biology · 2026Article
- Beyond the chaos: How architecture structures tumour biology.The FEBS journal · 2026Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer metastasis, i.e., the spreading of tumor cells from the primary tumor to distant organs, is responsible for the vast majority of cancer deaths. In the process, cancer cells migrate through narrow interstitial spaces substantially smaller in cross-section than the cell. During such confined migration, cancer cells experience extensive nuclear deformation, nuclear envelope rupture, and DNA damage. The molecular mechanisms responsible for the confined migration-induced DNA damage remain incompletely understood. Although in some cell lines, DNA damage is closely associated with nuclear envelope rupture, we show that, in others, mechanical deformation of the nucleus is sufficient to cause DNA damage, even in the absence of nuclear envelope rupture. This deformation-induced DNA damage, unlike nuclear-envelope-rupture-induced DNA damage, occurs primarily in S/G2 phase of the cell cycle and is associated with replication forks. Nuclear deformation, resulting from either confined migration or external cell compression, increases replication stress, possibly by increasing replication fork stalling, providing a molecular mechanism for the deformation-induced DNA damage. Thus, we have uncovered a new mechanism for mechanically induced DNA damage, linking mechanical deformation of the nucleus to DNA replication stress. This mechanically induced DNA damage could not only increase genomic instability in metastasizing cancer cells but could also cause DNA damage in non-migrating cells and tissues that experience mechanical compression during development, thereby contributing to tumorigenesis and DNA damage response activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.