ArticleCancer research2014
Bcl2 induces DNA replication stress by inhibiting ribonucleotide reductase.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Pooled it
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Cyclin D1 overexpression induces replication stress and microhomology-mediated end-joining dependence in mantle cell lymphoma.The Journal of clinical investigation · 2025Article
- The multiple activations in budding yeast S-phase checkpoint are Poisson processes.PNAS nexus · 2023Article
- dTMP imbalance through thymidylate 5'-phosphohydrolase activity induces apoptosis in triple-negative breast cancers.Scientific reports · 2022Article
- DNA damage responses that enhance resilience to replication stress.Cellular and molecular life sciences : CMLS · 2021Review
- A proteomic analysis of Bcl-2 regulation of cell cycle arrest: insight into the mechanisms.Journal of Zhejiang University. Science. B · 2021Article
- Histone dynamics during DNA replication stress.Journal of biomedical science · 2021Review
- MYC-Induced Replicative Stress: A Double-Edged Sword for Cancer Development and Treatment.International journal of molecular sciences · 2021Review
- Replication Stress, Genomic Instability, and Replication Timing: A Complex Relationship.International journal of molecular sciences · 2021Review
- Bcl2-induced DNA replication stress promotes lung carcinogenesis in response to space radiation.Carcinogenesis · 2020Article
- Review
- Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition.Oncogene · 2020Article
- Acetylation regulates ribonucleotide reductase activity and cancer cell growth.Nature communications · 2019Article
- DNA replication stress: oncogenes in the spotlight.Genetics and molecular biology · 2019Article
- Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place.Cancer discovery · 2018Review
- A comparison between lung carcinoma and a subcutaneous malignant tumor induced in rats by a 3,4-benzopyrene injection.International journal of clinical and experimental pathology · 2018Article
- Rescue from replication stress during mitosis.Cell cycle (Georgetown, Tex.) · 2017Review
- BH4 domain of Bcl-2 as a novel target for cancer therapy.Drug discovery today · 2016Review
- Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme.FEBS letters · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
DNA replication stress is an inefficient DNA synthesis process that leads replication forks to progress slowly or stall. Two main factors that cause replication stress are alterations in pools of deoxyribonucleotide (dNTP) precursors required for DNA synthesis and changes in the activity of proteins required for synthesis of dNTPs. Ribonucleotide reductase (RNR), containing regulatory hRRM1 and catalytic hRRM2 subunits, is the enzyme that catalyzes the conversion of ribonucleoside diphosphates (NDP) to deoxyribonucleoside diphosphates (dNDP) and thereby provides dNTP precursors needed for the synthesis of DNA. Here, we demonstrate that either endogenous or exogenous expression of Bcl2 results in decreases in RNR activity and intracellular dNTP, retardation of DNA replication fork progression, and increased rate of fork asymmetry leading to DNA replication stress. Bcl2 colocalizes with hRRM1 and hRRM2 in the cytoplasm and directly interacts via its BH4 domain with hRRM2 but not hRRM1. Removal of the BH4 domain of Bcl2 abrogates its inhibitory effects on RNR activity, dNTP pool level, and DNA replication. Intriguingly, Bcl2 directly inhibits RNR activity by disrupting the functional hRRM1/hRRM2 complex via its BH4 domain. Our findings argue that Bcl2 reduces intracellular dNTPs by inhibiting ribonucleotide reductase activity, thereby providing insight into how Bcl2 triggers DNA replication stress.
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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.