Nucleic Acid Immunity

Advances in immunology, Journal Year: 2016, Volume and Issue: unknown, P. 121 - 169

Published: Dec. 15, 2016

Language: Английский

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The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells

Proceedings of the National Academy of Sciences, Journal Year: 2013, Volume and Issue: 110(35), P. 14272 - 14277

Published: July 15, 2013

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 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 ubiquitous in organs. Here we identify general function regulation dNTP pools cultured cells. nuclear variably expressed during cell cycle, maximally quiescence minimally S-phase. Treatment lung or skin fibroblasts with specific siRNAs resulted disappearence accompanied loss cell-cycle pool sizes imbalance. Cells accumulated G1 phase oversized stopped growing. Following removal siRNA, were normalized growth restarted, but only after had reappeared. In quiescent cultures down-regulation leads marked expansion pools. all cases largest effect on dGTP, preferred substrate SAMHD1. Ribonucleotide reductase, responsible de novo synthesis dNTPs, cytosolic induced S-phase Thus, mammalian cells cycle two main enzymes controlling adjusted requirements replication. Synthesis reductase peaks S-phase, catabolism maximal when large would prevent from preparing new round

Language: Английский

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SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage

Blood, Journal Year: 2013, Volume and Issue: 123(7), P. 1021 - 1031

Published: Dec. 13, 2013

Language: Английский

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Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutières Syndrome and HIV-1 Restriction

Journal of Biological Chemistry, Journal Year: 2013, Volume and Issue: 288(12), P. 8101 - 8110

Published: Jan. 31, 2013

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

Language: Английский

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HIV-1 Latency in Monocytes/Macrophages

Viruses, Journal Year: 2014, Volume and Issue: 6(4), P. 1837 - 1860

Published: April 22, 2014

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and of the monocyte/macrophage lineage. HIV pathogenesis is characterized by depletion lymphocytes presence a population in which latency has been established called HIV-1 reservoir. Highly active antiretroviral therapy (HAART) significantly improved life infected patients. However, complete eradication from individuals not possible without targeting latent sources infection. establishes infection resting findings indicate that can also be Monocyte/macrophage lineage includes among others, monocytes, macrophages brain resident macrophages. These are relatively more resistant to apoptosis induced HIV-1, thus important stable hideouts virus. Much effort made direction eliminating T-cell reservoirs. it impossible achieve cure for considering these neglected reservoirs, In this review we will describe our current understanding mechanism how such specifically eliminated host.

Language: Английский

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