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SAMHD1 Functions and Human Diseases

1
Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30032, USA
2
Center for Drug Discovery, Children’s Healthcare of Atlanta, Atlanta, GA 30032, USA
*
Author to whom correspondence should be addressed.
These authors equally contributed.
Viruses 2020, 12(4), 382; https://doi.org/10.3390/v12040382
Received: 9 March 2020 / Revised: 27 March 2020 / Accepted: 28 March 2020 / Published: 31 March 2020
(This article belongs to the Special Issue Role of Myeloid Cells in Viral Infections)
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. View Full-Text
Keywords: SAMHD1; dNTPs; viruses; Aicardi–Goutières syndrome; cancers SAMHD1; dNTPs; viruses; Aicardi–Goutières syndrome; cancers
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Coggins, S.A.; Mahboubi, B.; Schinazi, R.F.; Kim, B. SAMHD1 Functions and Human Diseases. Viruses 2020, 12, 382.

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