ArticleMolecular cancer therapeutics2014
BRCA2 and RAD51 promote double-strand break formation and cell death in response to gemcitabine.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.Oncogene · 2025Article
- Pathogenic variants in MAEA disrupt DNA replication fork stability and are associated with developmental abnormalities in humans.Science advances · 2025Article
- CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549.Molecular & cellular oncology · 2025Article
- Article
- Cytidine deaminases APOBEC3C and APOBEC3D promote DNA replication stress resistance in pancreatic cancer cells.Nature cancer · 2024Article
- p21 promotes gemcitabine tolerance in A549 cells by inhibiting DNA damage and altering the cell cycle.Oncology letters · 2023Article
- Gemcitabine‑fucoxanthin combination in human pancreatic cancer cells.Biomedical reports · 2023Article
- Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas.International journal of molecular sciences · 2022Article
- The role of lncRNA-mediated ceRNA regulatory networks in pancreatic cancer.Cell death discovery · 2022Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.Molecular biology reports · 2021Review
- Overexpression of Interferon-Inducible Protein 16 Promotes Progression of Human Pancreatic Adenocarcinoma Through Interleukin-1β-Induced Tumor-Associated Macrophage Infiltration in the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Article
- Long Non-coding RNA DLEU2L Targets miR-210-3p to Suppress Gemcitabine Resistance in Pancreatic Cancer Cells via BRCA2 Regulation.Frontiers in molecular biosciences · 2021Article
- Review
- Compensatory combination of romidepsin with gemcitabine and cisplatin to effectively and safely control urothelial carcinoma.British journal of cancer · 2020Article
- Mre11 exonuclease activity removes the chain-terminating nucleoside analog gemcitabine from the nascent strand during DNA replication.Science advances · 2020Article
- The DNA repair helicase RECQ1 has a checkpoint-dependent role in mediating DNA damage responses induced by gemcitabine.The Journal of biological chemistry · 2019Article
- Non-enzymatic roles of human RAD51 at stalled replication forks.Nature communications · 2019Article
- MUS81 Participates in the Progression of Serous Ovarian Cancer Associated With Dysfunctional DNA Repair System.Frontiers in oncology · 2019Article
- Inactivation of XPF Sensitizes Cancer Cells to Gemcitabine.Journal of nucleic acids · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Replication inhibitors cause replication fork stalling and double-strand breaks (DSB) that result from processing of stalled forks. During recovery from replication blocks, the homologous recombination (HR) factor RAD51 mediates fork restart and DSB repair. HR defects therefore sensitize cells to replication inhibitors, with clear implications for cancer therapy. Gemcitabine is a potent replication inhibitor used to treat cancers with mutations in HR genes such as BRCA2. Here, we investigate why, paradoxically, mutations in HR genes protect cells from killing by gemcitabine. Using DNA replication and DNA damage assays in mammalian cells, we show that even short gemcitabine treatments cause persistent replication inhibition. BRCA2 and RAD51 are recruited to chromatin early after removal of the drug, actively inhibit replication fork progression, and promote the formation of MUS81- and XPF-dependent DSBs that remain unrepaired. Our data suggest that HR intermediates formed at gemcitabine-stalled forks are converted into DSBs and thus contribute to gemcitabine-induced cell death, which could have implications for the treatment response of HR-deficient tumors.
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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.