ArticleProceedings of the National Academy of Sciences of the United States of America2014
Conserved electron donor complex Dre2-Tah18 is required for ribonucleotide reductase metallocofactor assembly and DNA synthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Monothiol glutaredoxins in microbial iron metabolism: From iron-sulfur cluster trafficking to iron-dependent regulation.Advances in microbial physiology · 2026Review
- Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery.Cells · 2025Review
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- Tolerance to replication stress requires Dun1p kinase and activation of the electron transport chain.Biochimica et biophysica acta. Molecular cell research · 2023Article
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- The C-terminal domain of Hsp70 is responsible for paralog-specific regulation of ribonucleotide reductase.PLoS genetics · 2022Article
- Recent Advances in the Elucidation of Frataxin Biochemical Function Open Novel Perspectives for the Treatment of Friedreich's Ataxia.Frontiers in neuroscience · 2022Review
- Fungal phytochrome chromophore biosynthesis at mitochondria.The EMBO journal · 2021Article
- New Insights into the Role of Ferritin in Iron Homeostasis and Neurodegenerative Diseases.Molecular neurobiology · 2021Review
- Frataxin deficiency promotes endothelial senescence in pulmonary hypertension.The Journal of clinical investigation · 2021Article
- Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets.Annual review of biochemistry · 2020Review
- The Hsp70 co-chaperone Ydj1/HDJ2 regulates ribonucleotide reductase activity.PLoS genetics · 2018Article
- Activation of TNF-α/NF-κB axis enhances CRL4BMolecular oncology · 2018Article
- MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BMolecular therapy. Nucleic acids · 2018Article
- The diferric-tyrosyl radical cluster of ribonucleotide reductase and cytosolic iron-sulfur clusters have distinct and similar biogenesis requirements.The Journal of biological chemistry · 2017Article
- CRL4BScientific reports · 2017Article
- Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA Replication.Molecular cell · 2017Article
- Evolutionary conservation and in vitro reconstitution of microsporidian iron-sulfur cluster biosynthesis.Nature communications · 2017Article
- DNA Methylation Mediated Downregulation of miR-449c Controls Osteosarcoma Cell Cycle Progression by Directly Targeting Oncogene c-Myc.International journal of biological sciences · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Eukaryotic ribonucleotide reductases (RNRs) require a diferric-tyrosyl radical (Fe(III)2-Y•) cofactor to produce deoxynucleotides essential for DNA replication and repair. This metallocofactor is an important target of RNR-based therapeutics, although mechanisms of in vivo cofactor assembly, inactivation, and reactivation are poorly understood. Here, we demonstrate that the conserved Fe-S protein-diflavin reductase complex, Dre2-Tah18, plays a critical role in RNR cofactor biosynthesis. Depletion of Dre2 affects both RNR gene transcription and mRNA turnover through the activation of the DNA-damage checkpoint and the Aft1/Aft2-controlled iron regulon. Under conditions of comparable RNR protein levels, cells with diminishing Dre2 have significantly reduced ability to make deoxynucleotides. Furthermore, the kinetics and levels of in vivo reconstitution of the RNR cofactor are severely impaired in two conditional tah18 mutants. Together, these findings provide insight into RNR cofactor formation and reveal a shared mechanism underlying assembly of the Fe(III)2-Y• cofactor in RNR and the Fe-S clusters in cytosolic and nuclear proteins.
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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.