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SAMHD1 Functions and Human Diseases

Deoxynucleoside triphosphate (dNTP) molecules are essential for the replication and maintenance of genomic information in both cells and a variety of viral pathogens. While the process of dNTP biosynthesis by cellular enzymes, such as ribonucleotide reductase (RNR) and thymidine kinase (TK), has bee...

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Autores principales: Coggins, Si’Ana A., Mahboubi, Bijan, Schinazi, Raymond F., Kim, Baek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232136/
https://www.ncbi.nlm.nih.gov/pubmed/32244340
http://dx.doi.org/10.3390/v12040382
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author Coggins, Si’Ana A.
Mahboubi, Bijan
Schinazi, Raymond F.
Kim, Baek
author_facet Coggins, Si’Ana A.
Mahboubi, Bijan
Schinazi, Raymond F.
Kim, Baek
author_sort Coggins, Si’Ana A.
collection PubMed
description Deoxynucleoside triphosphate (dNTP) molecules are essential for the replication and maintenance of genomic information in both cells and a variety of viral pathogens. While the process of dNTP biosynthesis by cellular enzymes, such as ribonucleotide reductase (RNR) and thymidine kinase (TK), has been extensively investigated, a negative regulatory mechanism of dNTP pools was recently found to involve sterile alpha motif (SAM) domain and histidine-aspartate (HD) domain-containing protein 1, SAMHD1. When active, dNTP triphosphohydrolase activity of SAMHD1 degrades dNTPs into their 2′-deoxynucleoside (dN) and triphosphate subparts, steadily depleting intercellular dNTP pools. The differential expression levels and activation states of SAMHD1 in various cell types contributes to unique dNTP pools that either aid (i.e., dividing T cells) or restrict (i.e., nondividing macrophages) viral replication that consumes cellular dNTPs. Genetic mutations in SAMHD1 induce a rare inflammatory encephalopathy called Aicardi–Goutières syndrome (AGS), which phenotypically resembles viral infection. Recent publications have identified diverse roles for SAMHD1 in double-stranded break repair, genome stability, and the replication stress response through interferon signaling. Finally, a series of SAMHD1 mutations were also reported in various cancer cell types while why SAMHD1 is mutated in these cancer cells remains to investigated. Here, we reviewed a series of studies that have begun illuminating the highly diverse roles of SAMHD1 in virology, immunology, and cancer biology.
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spelling pubmed-72321362020-06-01 SAMHD1 Functions and Human Diseases Coggins, Si’Ana A. Mahboubi, Bijan Schinazi, Raymond F. Kim, Baek Viruses Review Deoxynucleoside triphosphate (dNTP) molecules are essential for the replication and maintenance of genomic information in both cells and a variety of viral pathogens. While the process of dNTP biosynthesis by cellular enzymes, such as ribonucleotide reductase (RNR) and thymidine kinase (TK), has been extensively investigated, a negative regulatory mechanism of dNTP pools was recently found to involve sterile alpha motif (SAM) domain and histidine-aspartate (HD) domain-containing protein 1, SAMHD1. When active, dNTP triphosphohydrolase activity of SAMHD1 degrades dNTPs into their 2′-deoxynucleoside (dN) and triphosphate subparts, steadily depleting intercellular dNTP pools. The differential expression levels and activation states of SAMHD1 in various cell types contributes to unique dNTP pools that either aid (i.e., dividing T cells) or restrict (i.e., nondividing macrophages) viral replication that consumes cellular dNTPs. Genetic mutations in SAMHD1 induce a rare inflammatory encephalopathy called Aicardi–Goutières syndrome (AGS), which phenotypically resembles viral infection. Recent publications have identified diverse roles for SAMHD1 in double-stranded break repair, genome stability, and the replication stress response through interferon signaling. Finally, a series of SAMHD1 mutations were also reported in various cancer cell types while why SAMHD1 is mutated in these cancer cells remains to investigated. Here, we reviewed a series of studies that have begun illuminating the highly diverse roles of SAMHD1 in virology, immunology, and cancer biology. MDPI 2020-03-31 /pmc/articles/PMC7232136/ /pubmed/32244340 http://dx.doi.org/10.3390/v12040382 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Coggins, Si’Ana A.
Mahboubi, Bijan
Schinazi, Raymond F.
Kim, Baek
SAMHD1 Functions and Human Diseases
title SAMHD1 Functions and Human Diseases
title_full SAMHD1 Functions and Human Diseases
title_fullStr SAMHD1 Functions and Human Diseases
title_full_unstemmed SAMHD1 Functions and Human Diseases
title_short SAMHD1 Functions and Human Diseases
title_sort samhd1 functions and human diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232136/
https://www.ncbi.nlm.nih.gov/pubmed/32244340
http://dx.doi.org/10.3390/v12040382
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