ArticleGenetics2016
Hydroxyurea Induces Cytokinesis Arrest in Cells Expressing a Mutated Sterol-14α-Demethylase in the Ergosterol Biosynthesis Pathway.
Article in Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- A tti1 mutation in the Tel2-Tti1-Tti2 complex specifically eliminates the cellular function of Rad3ATR, but not that of other PIKKs in fission yeast.PLoS genetics · 2026Article
- Temperature variability and other climatic attributes linked to genomic features in the lichen-forming fungal genus Umbilicaria.BMC biology · 2025Article
- Dissecting the Cell-Killing Mechanisms of Hydroxyurea Using Spot Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Characteristic effect of hydroxyurea on the higher-order structure of DNA and gene expression.Scientific reports · 2024Article
- Resumption of Spermatogenesis and Fertility Post Withdrawal of Hydroxyurea Treatment.International journal of molecular sciences · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.PLoS genetics · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.bioRxiv : the preprint server for biology · 2023Article
- The biological relevance of the FspTF transcription factor, homologous of Bqt4, inFrontiers in microbiology · 2023Article
- A missense mutation in themicroPublication biology · 2023Article
- Smc5/6 Complex Promotes Rad3Molecular and cellular biology · 2022Article
- Replication stress induced by the ribonucleotide reductase inhibitor guanazole, triapine and gemcitabine in fission yeast.FEMS yeast research · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Towards the Antiviral Agents and Nanotechnology-Enabled Approaches Against Parvovirus B19.Frontiers in cellular and infection microbiology · 2022Review
- Hydroxyurea-The Good, the Bad and the Ugly.Genes · 2021Review
- RecQ DNA Helicase Rqh1 Promotes Rad3Molecular and cellular biology · 2020Article
- Hydroxyurea-induced cutaneous squamous cell carcinoma: A case report.World journal of clinical cases · 2019Article
- AMolecular and cellular biology · 2019Article
- Novel Cell-Killing Mechanisms of Hydroxyurea and the Implication toward Combination Therapy for the Treatment of Fungal Infections.Antimicrobial agents and chemotherapy · 2017Article
- Heme deficiency sensitizes yeast cells to oxidative stress induced by hydroxyurea.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hydroxyurea (HU) has been used for the treatment of multiple diseases, such as cancer. The therapeutic effect is generally believed to be due to the suppression of ribonucleotide reductase (RNR), which slows DNA polymerase movement at replication forks and induces an S phase cell cycle arrest in proliferating cells. Although aberrant mitosis and DNA damage generated at collapsed forks are the likely causes of cell death in the mutants with defects in replication stress response, the mechanism underlying the cytotoxicity of HU in wild-type cells remains poorly understood. While screening for new fission yeast mutants that are sensitive to replication stress, we identified a novel mutation in the erg11 gene encoding the enzyme sterol-14α-demethylase in the ergosterol biosynthesis pathway that dramatically sensitizes the cells to chronic HU treatment. Surprisingly, HU mainly arrests the erg11 mutant cells in cytokinesis, not in S phase. Unlike the reversible S phase arrest in wild-type cells, the cytokinesis arrest induced by HU is relatively stable and occurs at low doses of the drug, which likely explains the remarkable sensitivity of the mutant to HU. We also show that the mutation causes sterol deficiency, which may predispose the cells to the cytokinesis arrest and lead to cell death. We hypothesize that in addition to the RNR, HU may have a secondary unknown target(s) inside cells. Identification of such a target(s) may greatly improve the chemotherapies that employ HU or help to expand the clinical usage of this drug for additional pathological conditions.
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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.