ArticleThe EMBO journal2023
Unrepaired base excision repair intermediates in template DNA strands trigger replication fork collapse and PARP inhibitor sensitivity.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Transcriptome-Based Synthetic Lethality Predictions to Improve Targeted Therapy/Immunotherapy Treatment Prioritization in Nonmetastatic Breast Cancer: BC-SELECT.Cancer research communications · 2026Article
- Optimizing transcriptome-based synthetic lethality predictions to improve targeted therapy / immunotherapy treatment prioritization in non-metastatic breast cancer: BC-SELECT.bioRxiv : the preprint server for biology · 2026Article
- Halogenated anthraquinones in breast cancer therapy: Structural modifications targeting VEGF-related angiogenesis pathways.Journal of pharmaceutical analysis · 2026Review
- Distinct repair outcomes from single and convergent replication fork collapse.Nature structural & molecular biology · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- A Bifunctional Antibody Conjugate for Marking the Location of DNA Binding Proteins on DNA Fibers.ACS omega · 2025Article
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer.Cancer science · 2025Article
- What is in a name? Rethinking SMUG1 in genome maintenance.NAR cancer · 2025Review
- The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage.Nucleic acids research · 2025Article
- HMCES corrupts replication fork stability during base excision repair in homologous recombination-deficient cells.Science advances · 2025Article
- CldU sensitizesFrontiers in oncology · 2025Article
- Positioning loss of PARP1 activity as the central toxic event in BRCA-deficient cancer.DNA repair · 2024Review
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Dispensability of HPF1 for cellular removal of DNA single-strand breaks.Nucleic acids research · 2024Article
- The dynamics and regulation of PARP1 and PARP2 in response to DNA damage and during replication.DNA repair · 2024Review
- Nucleolytic processing of abasic sites underlies PARP inhibitor hypersensitivity in ALC1-deficient BRCA mutant cancer cells.Nature communications · 2024Article
- Quantifying DNA replication speeds in single cells by scEdU-seq.Nature methods · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
DNA single-strand breaks (SSBs) disrupt DNA replication and induce chromosome breakage. However, whether SSBs induce chromosome breakage when present behind replication forks or ahead of replication forks is unclear. To address this question, we exploited an exquisite sensitivity of SSB repair-defective human cells lacking PARP activity or XRCC1 to the thymidine analogue 5-chloro-2'-deoxyuridine (CldU). We show that incubation with CldU in these cells results in chromosome breakage, sister chromatid exchange, and cytotoxicity by a mechanism that depends on the S phase activity of uracil DNA glycosylase (UNG). Importantly, we show that CldU incorporation in one cell cycle is cytotoxic only during the following cell cycle, when it is present in template DNA. In agreement with this, while UNG induces SSBs both in nascent strands behind replication forks and in template strands ahead of replication forks, only the latter trigger fork collapse and chromosome breakage. Finally, we show that BRCA-defective cells are hypersensitive to CldU, either alone and/or in combination with PARP inhibitor, suggesting that CldU may have clinical utility.
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What OpenQuestion holds
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.