ArticleProceedings of the National Academy of Sciences of the United States of America2010
Error-prone translesion synthesis mediates acquired chemoresistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 218 citations in OpenAlex.
- Replication stress in cancer: origins, consequences and therapeutic opportunities.Nature reviews. Cancer · 2026Review
- Docking-Based Virtual Screening Identifies a Small-Molecule Inhibitor of the Translesion Synthesis REV7/REV3 Protein-Protein Interaction.ChemMedChem · 2026Article
- Human REV1 interacts with DHX36 to promote replication and tolerance of G-quadruplex DNA.Nucleic acids research · 2026Article
- A mitochondrion-targeted natural polyphenolic copper carrier overcomes tumor resistance to cisplatin by potentiating cuproptosis.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting MAD2L2-dependent translesion synthesis impairs DNA damage tolerance and enhances cellular response to cisplatin.Frontiers in cell and developmental biology · 2026Article
- REV1 Loss Triggers a G2/M Cell-Cycle Arrest Through Dysregulation of Mitotic Regulators.Genes · 2025Article
- REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells.Oncology reports · 2025Article
- Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Key Nano-Strategies for Cisplatin Resistance in Advancing Anti-Cancer Therapy.International journal of nanomedicine · 2025Review
- Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer.iScience · 2024Article
- Probing hot spots of protein-protein interactions mediated by the safety-belt region of REV7.Structure (London, England : 1993) · 2024Article
- Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.Nature structural & molecular biology · 2024Article
- Small Cell Lung Cancer-An Update on Chemotherapy Resistance.Current treatment options in oncology · 2024Review
- REV1 coordinates a multi-faceted tolerance response to DNA alkylation damage and prevents chromosome shattering in Drosophila melanogaster.PLoS genetics · 2024Article
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
- Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.Cancer science · 2024Article
- Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer.Nucleic acids research · 2024Article
- REV7: a small but mighty regulator of genome maintenance and cancer development.Frontiers in oncology · 2024Review
83 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The development of cancer drug resistance is a persistent clinical problem limiting the successful treatment of disseminated malignancies. However, the molecular mechanisms by which initially chemoresponsive tumors develop therapeutic resistance remain poorly understood. Error-prone translesional DNA synthesis (TLS) is known to underlie the mutagenic effects of numerous anticancer agents, but little is known as to whether mutation induced by this process is ultimately relevant to tumor drug resistance. Here, we use a tractable mouse model of B-cell lymphoma to interrogate the role of error-prone translesional DNA synthesis in chemotherapy-induced mutation and resistance to front-line chemotherapy. We find that suppression of Rev1, an essential TLS scaffold protein and dCMP transferase, inhibits both cisplatin- and cyclophosphamide-induced mutagenesis. Additionally, by performing repeated cycles of tumor engraftment and treatment, we show that Rev1 plays a critical role in the development of acquired cyclophosphamide resistance. Thus, chemotherapy not only selects for drug-resistant tumor population but also directly promotes the TLS-mediated acquisition of resistance-causing mutations. These data provide an example of an alteration that prevents the acquisition of drug resistance in tumors in vivo. Because TLS also represents a critical mechanism of DNA synthesis in tumor cells following chemotherapy, these data suggest that TLS inhibition may have dual anticancer effects, sensitizing tumors to therapy as well as preventing the emergence of tumor chemoresistance.
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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.