Evidence map›Paper›PMID 23364794›Full record

ArticleThe Journal of biological chemistry2013

Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction.

Natalia Beloglazova, Robert Flick, Anatoli Tchigvintsev, Greg Brown, Ana Popovic, Boguslaw Nocek, Alexander F Yakunin

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
14.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

151 citing papers in PubMed, 215 citations in OpenAlex.

  1. Article
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91 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Natalia BeloglazovaDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Robert FlickDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Anatoli TchigvintsevDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Greg BrownDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Ana PopovicDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
Boguslaw NocekBioscience Division, Argonne National Laboratory, Argonne, Illinois 60439.
Alexander F YakuninDepartment of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E5, Canada. Electronic address: a.iakounine@utoronto.ca.
University of Toronto · CAArgonne National Laboratory · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human HD domain protein SAMHD1 is implicated in the Aicardi-Goutières autoimmune syndrome and in the restriction of HIV-1 replication in myeloid cells. Recently, this protein has been shown to possess dNTP triphosphatase activity, which is proposed to inhibit HIV-1 replication and the autoimmune response by hydrolyzing cellular dNTPs. Here, we show that the purified full-length human SAMHD1 protein also possesses metal-dependent 3'→5' exonuclease activity against single-stranded DNAs and RNAs in vitro. In double-stranded substrates, this protein preferentially cleaved 3'-overhangs and RNA in blunt-ended DNA/RNA duplexes. Full-length SAMHD1 also exhibited strong DNA and RNA binding to substrates with complex secondary structures. Both nuclease and dNTP triphosphatase activities of SAMHD1 are associated with its HD domain, but the SAM domain is required for maximal activity and nucleic acid binding. The nuclease activity of SAMHD1 could represent an additional mechanism contributing to HIV-1 restriction and suppression of the autoimmune response through direct cleavage of viral and endogenous nucleic acids. In addition, we demonstrated the presence of dGTP triphosphohydrolase and nuclease activities in several microbial HD domain proteins, suggesting that these proteins might contribute to antiviral defense in prokaryotes.

Indexed as

Amino Acid SubstitutionAutoimmune Diseases of the Nervous SystemCatalytic DomainDNA CleavageDNA, Single-StrandedExonucleasesgag Gene Products, Human Immunodeficiency VirusHIV-1HumansHydrolysisMagnesiumMolecular Sequence AnnotationMonomeric GTP-Binding ProteinsMutagenesis, Site-DirectedNervous System MalformationsProtein BindingDNA, Single-StrandedExonucleasesgag Gene Products, Human Immunodeficiency VirusMagnesiumMonomeric GTP-Binding ProteinsRNARNA, ViralSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, humantat Gene Products, Human Immunodeficiency Virus

Identifiers

PMID23364794
PMCPMC3605629
OpenAlexW2008892095

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.