ArticleNucleic acids research2022
Phosphorylation of SAMHD1 Thr592 increases C-terminal domain dynamics, tetramer dissociation and ssDNA binding kinetics.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed, 15 citations in OpenAlex.
- Nucleotide metabolic reprogramming: a "double-edged sword" in obesity-related inflammation-from metabolic adaptation to pathological imbalance.Journal of physiology and biochemistry · 2026Review
- p21 (CDKN1A) Is the Major Driver of Sulforaphane-Mediated Reduction in SAMHD1 T592 Phosphorylation in Macrophages.Biomolecules · 2026Article
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.Science (New York, N.Y.) · 2026Article
- Hepatocyte SAMHD1 Deficiency Attenuates Hepatic Steatosis via Suppression of SREBP Activation in a Mouse Model of Metabolic-Associated Steatotic Liver Disease.International journal of biological sciences · 2026Article
- ssDNA and ssRNA Promote Phase Condensation of SAMHD1.Biochemistry · 2025Article
- dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction.Journal of virology · 2025Review
- Article
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.Nucleic acids research · 2023Article
- Deoxyguanosine-Linked Bifunctional Inhibitor of SAMHD1 dNTPase Activity and Nucleic Acid Binding.ACS chemical biology · 2023Article
- Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells.Retrovirology · 2023Article
- SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks.Nature communications · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) is driven into its activated tetramer form by binding of GTP activator and dNTP activators/substrates. In addition, the inactive monomeric and dimeric forms of the enzyme bind to single-stranded (ss) nucleic acids. During DNA replication SAMHD1 can be phosphorylated by CDK1 and CDK2 at its C-terminal threonine 592 (pSAMHD1), localizing the enzyme to stalled replication forks (RFs) to promote their restart. Although phosphorylation has only a small effect on the dNTPase activity and ssDNA binding affinity of SAMHD1, perturbation of the native T592 by phosphorylation decreased the thermal stability of tetrameric SAMHD1 and accelerated tetramer dissociation in the absence and presence of ssDNA (∼15-fold). In addition, we found that ssDNA binds competitively with GTP to the A1 site. A full-length SAMHD1 cryo-EM structure revealed substantial dynamics in the C-terminal domain (which contains T592), which could be modulated by phosphorylation. We propose that T592 phosphorylation increases tetramer dynamics and allows invasion of ssDNA into the A1 site and the previously characterized DNA binding surface at the dimer-dimer interface. These features are consistent with rapid and regiospecific inactivation of pSAMHD1 dNTPase at RFs or other sites of free ssDNA in cells.
Indexed as
Identifiers
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.