ArticleNucleic acids research2015
Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
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- Dietary risk factors for lung cancer: an umbrella review of systematic review and meta-analysis.Translational cancer research · 2026Review
- Exploring the Role of Environmental Factors on Chromosomal Translocations Associated With Childhood Leukaemia.Cancer medicine · 2026Article
- Caffeine inhibits nonhomologous end joining by impairing ligase IV/XRCC4 function.Nucleic acids research · 2026Article
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- The Yeast HMGB Protein Hmo1 Is a Multifaceted Regulator of DNA Damage Tolerance.International journal of molecular sciences · 2025Article
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- Prolonged Cell Cycle Arrest in Response to DNA damage in Yeast Requires the Maintenance of DNA Damage Signaling and the Spindle Assembly Checkpoint.bioRxiv : the preprint server for biology · 2024Article
- An Improved Bulk DNA Extraction Method for Detection ofInsects · 2024Article
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- Proteasome-mediated degradation of long-range nucleases negatively regulates resection of DNA double-strand breaks.iScience · 2024Article
- Sir3 heterochromatin protein promotes non-homologous end joining by direct inhibition of Sae2.The EMBO journal · 2022Article
- Yap1-mediated Flr1 expression reveals crosstalk between oxidative stress signaling and caffeine resistance inFrontiers in microbiology · 2022Article
- Ecdysteroid kinase-like (EcKL) paralogs confer developmental tolerance to caffeine inCurrent research in insect science · 2022Article
- Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms.Journal of microbiology and biotechnology · 2021Review
- Autophagy as a Mechanism for Adaptive Prediction-Mediated Emergence of Drug Resistance.Frontiers in microbiology · 2021Article
- Review
- Quantitative mechanisms of DNA damage sensing and signaling.Current genetics · 2020Review
- Low dose ionizing radiation strongly stimulates insertional mutagenesis in a γH2AX dependent manner.PLoS genetics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In response to chromosomal double-strand breaks (DSBs), eukaryotic cells activate the DNA damage checkpoint, which is orchestrated by the PI3 kinase-like protein kinases ATR and ATM (Mec1 and Tel1 in budding yeast). Following DSB formation, Mec1 and Tel1 phosphorylate histone H2A on serine 129 (known as γ-H2AX). We used caffeine to inhibit the checkpoint kinases after DSB induction. We show that prolonged phosphorylation of H2A-S129 does not require continuous Mec1 and Tel1 activity. Unexpectedly, caffeine treatment impaired homologous recombination by inhibiting 5' to 3' end resection, independent of Mec1 and Tel1 inhibition. Caffeine treatment led to the rapid loss, by proteasomal degradation, of both Sae2, a nuclease that plays a role in early steps of resection, and Dna2, a nuclease that facilitates one of two extensive resection pathways. Sae2's instability is evident in the absence of DNA damage. A similar loss is seen when protein synthesis is inhibited by cycloheximide. Caffeine treatment had similar effects on irradiated HeLa cells, blocking the formation of RPA and Rad51 foci that depend on 5' to 3' resection of broken chromosome ends. Our findings provide insight toward the use of caffeine as a DNA damage-sensitizing agent in cancer cells.
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