ArticleMolecular cell2017
Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA Replication.
Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
- Sodium Sulfite as an Oxygen-Depletion-Based Chemical Model of Tumor Hypoxia In Vitro.Applied biochemistry and biotechnology · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Ribonucleotide Reductase Inhibition Overcomes FLT3 Inhibitor Resistance in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2026Article
- Harmane induces apoptosis through RRM2B and suppresses colorectal cancer progression.mSystems · 2026Article
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- Review
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.Combinatorial chemistry & high throughput screening · 2026Article
- Genetic dissection of Huntington's disease modification by variation at RRM2B.Human molecular genetics · 2025Article
- Characterizing and controlling CRISPR repair outcomes in nondividing human cells.Nature communications · 2025Article
- Bavachalcone targets transferrin receptor and sensitizes gemcitabine to affect bladder cancer progression.iMeta · 2025Article
- Lactylation-related gene signatures for prognosis and treatment response prediction in radiation-resistant non-small cell lung cancer.Discover oncology · 2025Article
- Blockade ofmBio · 2025Article
- Fuelling the Fight from the Gut: Short-Chain Fatty Acids and Dexamethasone Synergise to Suppress Gastric Cancer Cells.Cancers · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- Characterising Cancer Cell Responses to Cyclic Hypoxia Using Mathematical Modelling.Bulletin of mathematical biology · 2024Article
- Comprehensive analysis ofTranslational andrology and urology · 2024Article
- Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.Nature communications · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells exposed to hypoxia experience replication stress but do not accumulate DNA damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is the only enzyme capable of de novo synthesis of deoxyribonucleotide triphosphates (dNTPs). However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2 and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and therefore is favored over RRM1/RRM2 in order to preserve ongoing replication and avoid the accumulation of DNA damage. We found two distinct mechanisms by which RRM2B maintains hypoxic activity and identified responsible residues in RRM2B. The importance of RRM2B in the response to tumor hypoxia is further illustrated by correlation of its expression with a hypoxic signature in patient samples and its roles in tumor growth and radioresistance. Our data provide mechanistic insight into RNR biology, highlighting RRM2B as a hypoxic-specific, anti-cancer therapeutic target.
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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.