ArticleNature communications2019
Replication stress triggers microsatellite destabilization and hypermutation leading to clonal expansion in vitro.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
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- A small molecule disrupts G4-STAT1 interaction and synergizes with olaparib to drive cancer cell death.Nucleic acids research · 2026Article
- A pan-cancer analysis revealedPrecision clinical medicine · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- POLE Deficiency Exacerbates Diesel Engine Exhaust-Induced Genomic Instability and Malignant Transformation of Bronchial Epithelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors.NPJ precision oncology · 2024Review
- Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery.Scientific reports · 2024Observational
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- DSB profiles in human spermatozoa highlight the role of TMEJ in the male germline.Frontiers in genetics · 2024Article
- Marine Plasmalogens: A Gift from the Sea with Benefits for Age-Associated Diseases.Molecules (Basel, Switzerland) · 2023Review
- TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.Nature communications · 2023Article
- Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
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- Learning and Investigation of the Role of Angiotensin-Converting Enzyme in Radiotherapy for Nasopharyngeal Carcinoma.Biomedicines · 2023Article
- PANoptosis-based molecular subtyping and HPAN-index predicts therapeutic response and survival in hepatocellular carcinoma.Frontiers in immunology · 2023Article
- Microsatellite instability-related prognostic risk score (MSI-pRS) defines a subset of lung squamous cell carcinoma (LUSC) patients with genomic instability and poor clinical outcome.Frontiers in genetics · 2023Article
- Genome destabilization-associated phenotypes arising as a consequence of therapeutic treatment are suppressed by Olaparib.PloS one · 2023Article
- Echoed induction of nucleotide variants and chromosomal structural variants in cancer cells.Scientific reports · 2022Article
- KMT2C-deficient tumors have elevated APOBEC mutagenesis and genomic instability in multiple cancers.NAR cancer · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mismatch repair (MMR)-deficient cancers are characterized by microsatellite instability (MSI) and hypermutation. However, it remains unclear how MSI and hypermutation arise and contribute to cancer development. Here, we show that MSI and hypermutation are triggered by replication stress in an MMR-deficient background, enabling clonal expansion of cells harboring ARF/p53-module mutations and cells that are resistant to the anti-cancer drug camptothecin. While replication stress-associated DNA double-strand breaks (DSBs) caused chromosomal instability (CIN) in an MMR-proficient background, they induced MSI with concomitant suppression of CIN via a PARP-mediated repair pathway in an MMR-deficient background. This was associated with the induction of mutations, including cancer-driver mutations in the ARF/p53 module, via chromosomal deletions and base substitutions. Immortalization of MMR-deficient mouse embryonic fibroblasts (MEFs) in association with ARF/p53-module mutations was ~60-fold more efficient than that of wild-type MEFs. Thus, replication stress-triggered MSI and hypermutation efficiently lead to clonal expansion of cells with abrogated defense systems.
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