ArticleProceedings of the National Academy of Sciences of the United States of America2013
The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 264 citations in OpenAlex.
- Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance.Frontiers in cell and developmental biology · 2022Pooled it
- Nucleotide metabolic reprogramming: a "double-edged sword" in obesity-related inflammation-from metabolic adaptation to pathological imbalance.Journal of physiology and biochemistry · 2026Review
- The Role of SAMHD1 in Viral Resistance and Transduction Efficiency Challenges in Pediatric Hematological Malignancies: Mechanistic Insights and Clinical Perspectives.European journal of haematology · 2026Review
- Transition Metal Activation Reframes SAMHD1 Regulation.ACS chemical biology · 2026Article
- Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Article
- Bloom syndrome helicase is required for efficient HIV-1 reverse transcription in macrophages.bioRxiv : the preprint server for biology · 2026Article
- Transition metal activation reframes SAMHD1 regulation.bioRxiv : the preprint server for biology · 2026Article
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- Nucleotide salvage, genome instability, and potential therapeutic applications.Nucleic acids research · 2026Review
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières syndrome type 5: a case report and literature review.Frontiers in pediatrics · 2026Article
- Cellular pharmacology of fludarabine: molecular determinants of transport and metabolism.Frontiers in pharmacology · 2026Review
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Article
- High tide or low tide: the transport and metabolism of mitochondrial nucleotides.The Biochemical journal · 2025Review
- A deoxynucleoside triphosphate triphosphohydrolase promotes cell cycle progression inJournal of bacteriology · 2025Article
- Iron deficiency causes aspartate-sensitive dysfunction in CD8Nature communications · 2025Article
122 more citing papers are in PubMed but not listed here.
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8 authors at 1 institution in 1 country.
Funding
Abstract
Sterile alpha motif and HD-domain containing protein 1 (SAMHD1) is a triphosphohydrolase converting deoxynucleoside triphosphates (dNTPs) to deoxynucleosides. The enzyme was recently identified as a component of the human innate immune system that restricts HIV-1 infection by removing dNTPs required for viral DNA synthesis. SAMHD1 has deep evolutionary roots and is ubiquitous in human organs. Here we identify a general function of SAMHD1 in the regulation of dNTP pools in cultured human cells. The protein was nuclear and variably expressed during the cell cycle, maximally during quiescence and minimally during S-phase. Treatment of lung or skin fibroblasts with specific siRNAs resulted in the disappearence of SAMHD1 accompanied by loss of the cell-cycle regulation of dNTP pool sizes and dNTP imbalance. Cells accumulated in G1 phase with oversized pools and stopped growing. Following removal of the siRNA, the pools were normalized and cell growth restarted, but only after SAMHD1 had reappeared. In quiescent cultures SAMHD1 down-regulation leads to a marked expansion of dNTP pools. In all cases the largest effect was on dGTP, the preferred substrate of SAMHD1. Ribonucleotide reductase, responsible for the de novo synthesis of dNTPs, is a cytosolic enzyme maximally induced in S-phase cells. Thus, in mammalian cells the cell cycle regulation of the two main enzymes controlling dNTP pool sizes is adjusted to the requirements of DNA replication. Synthesis by the reductase peaks during S-phase, and catabolism by SAMHD1 is maximal during G1 phase when large dNTP pools would prevent cells from preparing for a new round of DNA replication.
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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.