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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Review Article

Is Uracil-DNA Glycosylase UNG2 a New Cellular Weapon Against HIV-1?

Author(s): Hesna Kara, Nathalie Chazal and Serge Bouaziz*

Volume 17, Issue 3, 2019

Page: [148 - 160] Pages: 13

DOI: 10.2174/1570162X17666190821154331

Price: $65

Abstract

Uracil-DNA glycosylase-2 (UNG2) is a DNA repair protein that removes uracil from single and double-stranded DNA through a basic excision repair process. UNG2 is packaged into new virions by interaction with integrase (IN) and is needed during the early stages of the replication cycle. UNG2 appears to play both a positive and negative role during HIV-1 replication; UNG2 improves the fidelity of reverse transcription but the nuclear isoform of UNG2 participates in the degradation of cDNA and the persistence of the cellular genome by repairing its uracil mismatches. In addition, UNG2 is neutralized by Vpr, which redirects it to the proteasome for degradation, suggesting that UNG2 may be a new cellular restriction factor. So far, we have not understood why HIV-1 imports UNG2 via its IN and why it causes degradation of endogenous UNG2 by redirecting it to the proteasome via Vpr. In this review, we propose to discuss the ambiguous role of UNG2 during the HIV-1 replication cycle.

Keywords: HIV-1, UNG2, Vpr, replication, BER, UDGs, uracil.

Graphical Abstract
[1]
Olinski R, Jurgowiak M, Zaremba T. Uracil in DNA--its biological significance. Mutat Res 2010; 705(3): 239-45.
[http://dx.doi.org/10.1016/j.mrrev.2010.08.001] [PMID: 20709185]
[2]
Ladner RD, Caradonna SJ. The human dUTPase gene encodes both nuclear and mitochondrial isoforms. Differential expression of the isoforms and characterization of a cDNA encoding the mitochondrial species. J Biol Chem 1997; 272(30): 19072-80.
[http://dx.doi.org/10.1074/jbc.272.30.19072] [PMID: 9228092]
[3]
Auerbach P, Bennett RAO, Bailey EA, Krokan HE, Demple B. Mutagenic specificity of endogenously generated abasic sites in Saccharomyces cerevisiae chromosomal DNA. Proc Natl Acad Sci USA 2005; 102(49): 17711-6.
[http://dx.doi.org/10.1073/pnas.0504643102] [PMID: 16314579]
[4]
Duncan BK, Miller JH. Mutagenic deamination of cytosine residues in DNA. Nature 1980; 287(5782): 560-1.
[http://dx.doi.org/10.1038/287560a0] [PMID: 6999365]
[5]
Barnes DE, Lindahl T. Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 2004; 38: 445-76.
[http://dx.doi.org/10.1146/annurev.genet.38.072902.092448] [PMID: 15568983]
[6]
Hagen L, Peña-Diaz J, Kavli B, Otterlei M, Slupphaug G, Krokan HE. Genomic uracil and human disease. Exp Cell Res 2006; 312(14): 2666-72.
[http://dx.doi.org/10.1016/j.yexcr.2006.06.015] [PMID: 16860315]
[7]
Sousa MML, Krokan HE, Slupphaug G. DNA-uracil and human pathology. Mol Aspects Med 2007; 28(3-4): 276-306.
[http://dx.doi.org/10.1016/j.mam.2007.04.006] [PMID: 17590428]
[8]
Bessman MJ, Lehman IR, Adler J, Zimmerman SB, Simms ES, Kornberg A. Enzymatic synthesis of deoxyribonucleic acid III. The incorporation of pyrimidine and purine analogues into deoxyribonucleic acid. Proc Natl Acad Sci USA 1958; 44(7): 633-40.
[http://dx.doi.org/10.1073/pnas.44.7.633] [PMID: 16590253]
[9]
Focher F, Verri A, Verzeletti S, Mazzarello P, Spadari S. Uracil in OriS of herpes simplex 1 alters its specific recognition by origin binding protein (OBP): Does virus induced uracil-DNA glycosylase play a key role in viral reactivation and replication? Chromosoma 1992; 102(1)(Suppl.): S67-71.
[http://dx.doi.org/10.1007/BF02451788] [PMID: 1337882]
[10]
el-Hajj HH, Zhang H, Weiss B. Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli. J Bacteriol 1988; 170(3): 1069-75.
[http://dx.doi.org/10.1128/jb.170.3.1069-1075.1988] [PMID: 2830228]
[11]
Mosbaugh DW. Purification and characterization of porcine liver DNA polymerase gamma: Utilization of dUTP and dTTP during in vitro DNA synthesis. Nucleic Acids Res 1988; 16(12): 5645-59.
[http://dx.doi.org/10.1093/nar/16.12.5645] [PMID: 3387242]
[12]
Mosbaugh DW, Bennett SE. Uracil-excision DNA repair. Prog Nucleic Acid Res Mol Biol 1994; 48: 315-70.
[http://dx.doi.org/10.1016/S0079-6603(08)60859-4] [PMID: 7938553]
[13]
Aquaro S, Bagnarelli P, Guenci T, et al. Long-term survival and virus production in human primary macrophages infected by human immunodeficiency virus. J Med Virol 2002; 68(4): 479-88.
[http://dx.doi.org/10.1002/jmv.10245] [PMID: 12376954]
[14]
Aquaro S, Caliò R, Balzarini J, Bellocchi MC, Garaci E, Perno CF. Macrophages and HIV infection: Therapeutical approaches toward this strategic virus reservoir. Antiviral Res 2002; 55(2): 209-25.
[http://dx.doi.org/10.1016/S0166-3542(02)00052-9] [PMID: 12103427]
[15]
Cedergren-Zeppezauer ES, Larsson G, Nyman PO, Dauter Z, Wilson KS. Crystal structure of a dUTPase. Nature 1992; 355(6362): 740-3.
[http://dx.doi.org/10.1038/355740a0] [PMID: 1311056]
[16]
Hokari S, Sakagishi Y. Purification and characterization of deoxyuridine triphosphate nucleotidohydrolase from anemic rat spleen: a trimer composition of the enzyme protein. Arch Biochem Biophys 1987; 253(2): 350-6.
[http://dx.doi.org/10.1016/0003-9861(87)90188-3] [PMID: 3032103]
[17]
Hokari S, Takizawa A, Tanaka M, Sakagishi Y. Calf thymus deoxyuridine triphosphatase differs from rat spleen enzyme in molecular disposition. Biochem Int 1989; 19(3): 453-61.
[PMID: 2554912]
[18]
Giroir LE, Deutsch WA. Drosophila deoxyuridine triphosphatase. Purification and characterization. J Biol Chem 1987; 262(1): 130-4.
[PMID: 3025197]
[19]
Gadsden MH, McIntosh EM, Game JC, Wilson PJ, Haynes RH. dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. EMBO J 1993; 12(11): 4425-31.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb06127.x] [PMID: 8223452]
[20]
Pardo EG, Gutiérrez C. Cell cycle- and differentiation stage-dependent variation of dUTPase activity in higher plant cells. Exp Cell Res 1990; 186(1): 90-8.
[http://dx.doi.org/10.1016/0014-4827(90)90214-U] [PMID: 2153555]
[21]
Krokan HE, Drabløs F, Slupphaug G. Uracil in DNA--occurrence, consequences and repair. Oncogene 2002; 21(58): 8935-48.
[http://dx.doi.org/10.1038/sj.onc.1205996] [PMID: 12483510]
[22]
Liu M, Schatz DG. Balancing AID and DNA repair during somatic hypermutation. Trends Immunol 2009; 30(4): 173-81.
[http://dx.doi.org/10.1016/j.it.2009.01.007] [PMID: 19303358]
[23]
Zhang Q-M, Dianov GL. DNA repair fidelity of base excision repair pathways in human cell extracts. DNA Repair (Amst) 2005; 4(2): 263-70.
[http://dx.doi.org/10.1016/j.dnarep.2004.10.004] [PMID: 15590334]
[24]
Dianov G, Price A, Lindahl T. Generation of single-nucleotide repair patches following excision of uracil residues from DNA. Mol Cell Biol 1992; 12(4): 1605-12.
[http://dx.doi.org/10.1128/MCB.12.4.1605] [PMID: 1549115]
[25]
Dianov GL, Souza-Pinto N, Nyaga SG, Thybo T, Stevnsner T, Bohr VA. Base excision repair in nuclear and mitochondrial DNA. Prog Nucleic Acid Res Mol Biol 2001; 68: 285-97.
[http://dx.doi.org/10.1016/S0079-6603(01)68107-8] [PMID: 11554304]
[26]
Dianov GL, Sleeth KM, Dianova II, Allinson SL. Repair of abasic sites in DNA. Mutat Res 2003; 531(1-2): 157-63.
[http://dx.doi.org/10.1016/j.mrfmmm.2003.09.003] [PMID: 14637252]
[27]
Akbari M, Peña-Diaz J, Andersen S, Liabakk N-B, Otterlei M, Krokan HE. Extracts of proliferating and non-proliferating human cells display different base excision pathways and repair fidelity. DNA Repair (Amst) 2009; 8(7): 834-43.
[http://dx.doi.org/10.1016/j.dnarep.2009.04.002] [PMID: 19442590]
[28]
Vollberg TM, Lee KA, Sirover MA. Positive correlation between the extent of cell proliferation and the regulation of base excision repair. Cancer Res 1984; 44(6): 2377-81.
[PMID: 6722777]
[29]
Wang Z, Wu X, Friedberg EC. Molecular mechanism of base excision repair of uracil-containing DNA in yeast cell-free extracts. J Biol Chem 1997; 272(38): 24064-71.
[http://dx.doi.org/10.1074/jbc.272.38.24064] [PMID: 9295360]
[30]
Zharkov DO. Base excision DNA repair. Cell Mol Life Sci 2008; 65(10): 1544-65.
[http://dx.doi.org/10.1007/s00018-008-7543-2] [PMID: 18259689]
[31]
Parlanti E, Locatelli G, Maga G, Dogliotti E. Human base excision repair complex is physically associated to DNA replication and cell cycle regulatory proteins. Nucleic Acids Res 2007; 35(5): 1569-77.
[http://dx.doi.org/10.1093/nar/gkl1159] [PMID: 17289756]
[32]
Krokan HE, Nilsen H, Skorpen F, Otterlei M, Slupphaug G. Base excision repair of DNA in mammalian cells. FEBS Lett 2000; 476(1-2): 73-7.
[http://dx.doi.org/10.1016/S0014-5793(00)01674-4] [PMID: 10878254]
[33]
Kruman II, Schwartz E, Kruman Y, et al. Suppression of uracil-DNA glycosylase induces neuronal apoptosis. J Biol Chem 2004; 279(42): 43952-60.
[http://dx.doi.org/10.1074/jbc.M408025200] [PMID: 15297456]
[34]
Wilson DM III, Bohr VA. The mechanics of base excision repair, and its relationship to aging and disease. DNA Repair (Amst) 2007; 6(4): 544-59.
[http://dx.doi.org/10.1016/j.dnarep.2006.10.017] [PMID: 17112792]
[35]
Bulgar AD, Weeks LD, Miao Y, et al. Removal of uracil by uracil DNA glycosylase limits pemetrexed cytotoxicity: overriding the limit with methoxyamine to inhibit base excision repair. Cell Death Dis 2012; 3e252
[http://dx.doi.org/10.1038/cddis.2011.135] [PMID: 22237209]
[36]
Frosina G. Counteracting spontaneous transformation via overexpression of rate-limiting DNA base excision repair enzymes. Carcinogenesis 2001; 22(9): 1335-41.
[http://dx.doi.org/10.1093/carcin/22.9.1335] [PMID: 11532852]
[37]
Frosina G. Tumor suppression by DNA base excision repair. Mini Rev Med Chem 2007; 7(7): 727-43.
[http://dx.doi.org/10.2174/138955707781024544] [PMID: 17627584]
[38]
Friedberg EC. A history of the DNA repair and mutagenesis field: The discovery of base excision repair. DNA Repair (Amst) 2016; 37: A35-9.
[http://dx.doi.org/10.1016/j.dnarep.2015.12.003] [PMID: 26861186]
[39]
Lindahl T. My journey to DNA repair. Genomics Proteomics Bioinformatics 2013; 11(1): 2-7.
[http://dx.doi.org/10.1016/j.gpb.2012.12.001] [PMID: 23453014]
[40]
Nilsen H, Otterlei M, Haug T, et al. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene. Nucleic Acids Res 1997; 25(4): 750-5.
[http://dx.doi.org/10.1093/nar/25.4.750] [PMID: 9016624]
[41]
Baute J, Depicker A. Base excision repair and its role in maintaining genome stability. Crit Rev Biochem Mol Biol 2008; 43(4): 239-76.
[http://dx.doi.org/10.1080/10409230802309905] [PMID: 18756381]
[42]
Visnes T, Doseth B, Pettersen HS, et al. Uracil in DNA and its processing by different DNA glycosylases. Philos Trans R Soc Lond B Biol Sci 2009; 364(1517): 563-8.
[http://dx.doi.org/10.1098/rstb.2008.0186] [PMID: 19008197]
[43]
Schormann N, Ricciardi R, Chattopadhyay D. Uracil-DNA glycosylases-structural and functional perspectives on an essential family of DNA repair enzymes. Protein Sci 2014; 23(12): 1667-85.
[http://dx.doi.org/10.1002/pro.2554] [PMID: 25252105]
[44]
Akbari M, Otterlei M, Peña-Diaz J, Krokan HE. Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress. Neuroscience 2007; 145(4): 1201-12.
[http://dx.doi.org/10.1016/j.neuroscience.2006.10.010] [PMID: 17101234]
[45]
Caradonna S, Muller-Weeks S. The nature of enzymes involved in uracil-DNA repair: Isoform characteristics of proteins responsible for nuclear and mitochondrial genomic integrity. Curr Protein Pept Sci 2001; 2(4): 335-47.
[http://dx.doi.org/10.2174/1389203013381044] [PMID: 12369930]
[46]
Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA. A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 1996; 384(6604): 87-92.
[http://dx.doi.org/10.1038/384087a0] [PMID: 8900285]
[47]
Kara H, Ponchon L, Bouaziz S. Backbone resonance assignment of the human uracil DNA glycosylase-2. Biomol NMR Assign 2018; 12(1): 37-42.
[http://dx.doi.org/10.1007/s12104-017-9776-1] [PMID: 28940147]
[48]
Buchinger E, Wiik SÅ, Kusnierczyk A, et al. Backbone 1H, 13C and 15N chemical shift assignment of full-length human uracil DNA glycosylase UNG2. Biomol NMR Assign 2018; 12(1): 15-22.
[http://dx.doi.org/10.1007/s12104-017-9772-5] [PMID: 28879561]
[49]
Krokan HE, Otterlei M, Nilsen H, et al. Properties and functions of human uracil-DNA glycosylase from the UNG gene. Prog Nucleic Acid Res Mol Biol 2001; 68: 365-86.
[http://dx.doi.org/10.1016/S0079-6603(01)68112-1] [PMID: 11554311]
[50]
Leiros I, Moe E, Smalås AO, McSweeney S. Structure of the uracil-DNA N-glycosylase (UNG) from Deinococcus radiodurans. Acta Crystallogr D Biol Crystallogr 2005; 61(Pt 8): 1049-56.
[http://dx.doi.org/10.1107/S090744490501382X] [PMID: 16041069]
[51]
Mol CD, Arvai AS, Slupphaug G, et al. Crystal structure and mutational analysis of human uracil-DNA glycosylase: Structural basis for specificity and catalysis. Cell 1995; 80(6): 869-78.
[http://dx.doi.org/10.1016/0092-8674(95)90290-2] [PMID: 7697717]
[52]
Krokan HE, Standal R, Slupphaug G. DNA glycosylases in the base excision repair of DNA. Biochem J 1997; 325(Pt 1): 1-16.
[http://dx.doi.org/10.1042/bj3250001] [PMID: 9224623]
[53]
Zharkov DO, Mechetin GV, Nevinsky GA. Uracil-DNA glycosylase: Structural, thermodynamic and kinetic aspects of lesion search and recognition. Mutat Res 2010; 685(1-2): 11-20.
[http://dx.doi.org/10.1016/j.mrfmmm.2009.10.017] [PMID: 19909758]
[54]
Schonhoft JD, Kosowicz JG, Stivers JT. DNA translocation by human uracil DNA glycosylase: role of DNA phosphate charge. Biochemistry 2013; 52(15): 2526-35.
[http://dx.doi.org/10.1021/bi301561d] [PMID: 23506309]
[55]
Pearl LH. Structure and function in the uracil-DNA glycosylase superfamily. Mutat Res 2000; 460(3-4): 165-81.
[http://dx.doi.org/10.1016/S0921-8777(00)00025-2] [PMID: 10946227]
[56]
Eftedal I, Guddal PH, Slupphaug G, Volden G, Krokan HE. Consensus sequences for good and poor removal of uracil from double stranded DNA by uracil-DNA glycosylase. Nucleic Acids Res 1993; 21(9): 2095-101.
[http://dx.doi.org/10.1093/nar/21.9.2095] [PMID: 8502549]
[57]
Nakamura N, Morinaga H, Kikuchi M, et al. Cloning and characterization of uracil-DNA glycosylase and the biological consequences of the loss of its function in the nematode Caenorhabditis elegans. Mutagenesis 2008; 23(5): 407-13.
[http://dx.doi.org/10.1093/mutage/gen030] [PMID: 18524757]
[58]
Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J 1998; 17(17): 5214-26.
[http://dx.doi.org/10.1093/emboj/17.17.5214] [PMID: 9724657]
[59]
Visnes T, Akbari M, Hagen L, Slupphaug G, Krokan HE. The rate of base excision repair of uracil is controlled by the initiating glycosylase. DNA Repair (Amst) 2008; 7(11): 1869-81.
[http://dx.doi.org/10.1016/j.dnarep.2008.07.012] [PMID: 18721906]
[60]
Doseth B, Ekre C, Slupphaug G, Krokan HE, Kavli B. Strikingly different properties of uracil-DNA glycosylases UNG2 and SMUG1 may explain divergent roles in processing of genomic uracil. DNA Repair (Amst) 2012; 11(6): 587-93.
[http://dx.doi.org/10.1016/j.dnarep.2012.03.003] [PMID: 22483865]
[61]
Fischer JA, Caradonna SJ. Analysis of Nuclear Uracil DNA-Glycosylase (nUDG) Turnover During the Cell Cycle. Methods Mol Biol 2017; 1524: 177-88.
[http://dx.doi.org/10.1007/978-1-4939-6603-5_11] [PMID: 27815903]
[62]
Liu P, Burdzy A, Sowers LC. Substrate recognition by a family of uracil-DNA glycosylases: UNG, MUG, and TDG. Chem Res Toxicol 2002; 15(8): 1001-9.
[http://dx.doi.org/10.1021/tx020030a] [PMID: 12184783]
[63]
Friedberg EC, Walker GC, Siede W. DNA Repair and Mutagenesis. Washington, DC: ASM Press 1995.
[64]
Verri A, Mazzarello P, Spadari S, Focher F. Uracil-DNA glycosylases preferentially excise mispaired uracil. Biochem J 1992; 287(Pt 3): 1007-10.
[http://dx.doi.org/10.1042/bj2871007] [PMID: 1359874]
[65]
Nilsen H, Rosewell I, Robins P, et al. Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. Mol Cell 2000; 5(6): 1059-65.
[http://dx.doi.org/10.1016/S1097-2765(00)80271-3] [PMID: 10912000]
[66]
Pettersen HS, Sundheim O, Gilljam KM, Slupphaug G, Krokan HE, Kavli B. Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms. Nucleic Acids Res 2007; 35(12): 3879-92.
[http://dx.doi.org/10.1093/nar/gkm372] [PMID: 17537817]
[67]
Jacobs AL, Schär P. DNA glycosylases: in DNA repair and beyond. Chromosoma 2012; 121(1): 1-20.
[http://dx.doi.org/10.1007/s00412-011-0347-4] [PMID: 22048164]
[68]
Kavli B, Sundheim O, Akbari M, et al. hUNG2 is the major repair enzyme for removal of uracil from U: A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. J Biol Chem 2002; 277(42): 39926-36.
[http://dx.doi.org/10.1074/jbc.M207107200] [PMID: 12161446]
[69]
Lee D-H, Liu Y, Lee H-W, et al. A structural determinant in the uracil DNA glycosylase superfamily for the removal of uracil from adenine/uracil base pairs. Nucleic Acids Res 2015; 43(2): 1081-9.
[http://dx.doi.org/10.1093/nar/gku1332] [PMID: 25550433]
[70]
Hardeland U, Kunz C, Focke F, Szadkowski M, Schär P. Cell cycle regulation as a mechanism for functional separation of the apparently redundant uracil DNA glycosylases TDG and UNG2. Nucleic Acids Res 2007; 35(11): 3859-67.
[http://dx.doi.org/10.1093/nar/gkm337] [PMID: 17526518]
[71]
Abdel-Rahman WM, Knuutila S, Peltomäki P, Harrison DJ, Bader SA. Truncation of MBD4 predisposes to reciprocal chromosomal translocations and alters the response to therapeutic agents in colon cancer cells. DNA Repair (Amst) 2008; 7(2): 321-8.
[http://dx.doi.org/10.1016/j.dnarep.2007.11.009] [PMID: 18162445]
[72]
Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Nature 1999; 401(6750): 301-4.
[http://dx.doi.org/10.1038/45843] [PMID: 10499592]
[73]
Chen R, Wang H, Mansky LM. Roles of uracil-DNA glycosylase and dUTPase in virus replication. J Gen Virol 2002; 83(Pt 10): 2339-45.
[http://dx.doi.org/10.1099/0022-1317-83-10-2339] [PMID: 12237414]
[74]
Schormann N, Zhukovskaya N, Bedwell G, et al. Poxvirus uracil-DNA glycosylase-An unusual member of the family I uracil-DNA glycosylases. Protein Sci 2016; 25(12): 2113-31.
[http://dx.doi.org/10.1002/pro.3058] [PMID: 27684934]
[75]
Stuart DT, Upton C, Higman MA, Niles EG, McFadden G. A poxvirus-encoded uracil DNA glycosylase is essential for virus viability. J Virol 1993; 67(5): 2503-12.
[PMID: 8474156]
[76]
Pyles RB, Thompson RL. Evidence that the herpes simplex virus type 1 uracil DNA glycosylase is required for efficient viral replication and latency in the murine nervous system. J Virol 1994; 68(8): 4963-72.
[PMID: 8035495]
[77]
Bergman AC, Björnberg O, Nord J, Nyman PO, Rosengren AM. The protein p30, encoded at the gag-pro junction of mouse mammary tumor virus, is a dUTPase fused with a nucleocapsid protein. Virology 1994; 204(1): 420-4.
[http://dx.doi.org/10.1006/viro.1994.1547] [PMID: 8091672]
[78]
Elder JH, Lerner DL, Hasselkus-Light CS, et al. Distinct subsets of retroviruses encode dUTPase. J Virol 1992; 66(3): 1791-4.
[PMID: 1310783]
[79]
McGeoch DJ. Protein sequence comparisons show that the ‘pseudoproteases’ encoded by poxviruses and certain retroviruses belong to the deoxyuridine triphosphatase family. Nucleic Acids Res 1990; 18(14): 4105-10.
[http://dx.doi.org/10.1093/nar/18.14.4105] [PMID: 2165588]
[80]
Turelli P, Guiguen F, Mornex JF, Vigne R, Quérat G. dUTPase-minus caprine arthritis-encephalitis virus is attenuated for pathogenesis and accumulates G-to-A substitutions. J Virol 1997; 71(6): 4522-30.
[PMID: 9151845]
[81]
Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002; 418(6898): 646-50.
[http://dx.doi.org/10.1038/nature00939] [PMID: 12167863]
[82]
Sire J, Quérat G, Esnault C, Priet S. Uracil within DNA: an actor of antiviral immunity. Retrovirology 2008; 5: 45.
[http://dx.doi.org/10.1186/1742-4690-5-45] [PMID: 18533995]
[83]
Bouhamdan M, Benichou S, Rey F, et al. Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme. J Virol 1996; 70(2): 697-704.
[PMID: 8551605]
[84]
Cohen EA, Dehni G, Sodroski JG, Haseltine WA. Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol 1990; 64(6): 3097-9.
[PMID: 2139896]
[85]
Agostini I, Navarro JM, Rey F, et al. The human immunodeficiency virus type 1 Vpr transactivator: cooperation with promoter-bound activator domains and binding to TFIIB. J Mol Biol 1996; 261(5): 599-606.
[http://dx.doi.org/10.1006/jmbi.1996.0485] [PMID: 8800208]
[86]
Bukrinsky MI, Sharova N, Dempsey MP, et al. Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. Proc Natl Acad Sci USA 1992; 89(14): 6580-4.
[http://dx.doi.org/10.1073/pnas.89.14.6580] [PMID: 1631159]
[87]
Heinzinger NK, Bukrinsky MI, Haggerty SA, et al. The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells. Proc Natl Acad Sci USA 1994; 91(15): 7311-5.
[http://dx.doi.org/10.1073/pnas.91.15.7311] [PMID: 8041786]
[88]
Popov S, Rexach M, Zybarth G, et al. Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J 1998; 17(4): 909-17.
[http://dx.doi.org/10.1093/emboj/17.4.909] [PMID: 9463369]
[89]
He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol 1995; 69(11): 6705-11.
[PMID: 7474080]
[90]
Jowett JB, Planelles V, Poon B, Shah NP, Chen ML, Chen IS. The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle. J Virol 1995; 69(10): 6304-13.
[PMID: 7666531]
[91]
Laguette N, Brégnard C, Hue P, et al. Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. Cell 2014; 156(1-2): 134-45.
[http://dx.doi.org/10.1016/j.cell.2013.12.011] [PMID: 24412650]
[92]
Rogel ME, Wu LI, Emerman M. The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection. J Virol 1995; 69(2): 882-8.
[PMID: 7815556]
[93]
Sharifi HJ, Furuya AM, de Noronha CMC. The role of HIV-1 Vpr in promoting the infection of nondividing cells and in cell cycle arrest. Curr Opin HIV AIDS 2012; 7(2): 187-94.
[http://dx.doi.org/10.1097/COH.0b013e32835049e0] [PMID: 22274659]
[94]
Wu Y, Zhou X, Barnes CO, et al. The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nat Struct Mol Biol 2016; 23(10): 933-40.
[http://dx.doi.org/10.1038/nsmb.3284] [PMID: 27571178]
[95]
Briggs JAG, Simon MN, Gross I, et al. The stoichiometry of Gag protein in HIV-1. Nat Struct Mol Biol 2004; 11(7): 672-5.
[http://dx.doi.org/10.1038/nsmb785] [PMID: 15208690]
[96]
Müller B, Tessmer U, Schubert U, Kräusslich HG. Human immunodeficiency virus type 1 Vpr protein is incorporated into the virion in significantly smaller amounts than gag and is phosphorylated in infected cells. J Virol 2000; 74(20): 9727-31.
[http://dx.doi.org/10.1128/JVI.74.20.9727-9731.2000] [PMID: 11000245]
[97]
Mahalingam S, Khan SA, Jabbar MA, Monken CE, Collman RG, Srinivasan A. Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation. Virology 1995; 207(1): 297-302.
[http://dx.doi.org/10.1006/viro.1995.1081] [PMID: 7871742]
[98]
Bachand F, Yao XJ, Hrimech M, Rougeau N, Cohen EA. Incorporation of Vpr into human immunodeficiency virus type 1 requires a direct interaction with the p6 domain of the p55 gag precursor. J Biol Chem 1999; 274(13): 9083-91.
[http://dx.doi.org/10.1074/jbc.274.13.9083] [PMID: 10085158]
[99]
de Rocquigny H, Petitjean P, Tanchou V, et al. The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr. J Biol Chem 1997; 272(49): 30753-9.
[http://dx.doi.org/10.1074/jbc.272.49.30753] [PMID: 9388214]
[100]
Kondo E, Mammano F, Cohen EA, Göttlinger HG. The p6gag domain of human immunodeficiency virus type 1 is sufficient for the incorporation of Vpr into heterologous viral particles. J Virol 1995; 69(5): 2759-64.
[PMID: 7707498]
[101]
Lavallée C, Yao XJ, Ladha A, Göttlinger H, Haseltine WA, Cohen EA. Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles. J Virol 1994; 68(3): 1926-34.
[PMID: 8107252]
[102]
Willetts KE, Rey F, Agostini I, et al. DNA repair enzyme uracil DNA glycosylase is specifically incorporated into human immunodeficiency virus type 1 viral particles through a Vpr-independent mechanism. J Virol 1999; 73(2): 1682-8.
[PMID: 9882380]
[103]
Mansky LM, Preveral S, Selig L, Benarous R, Benichou S. The interaction of vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 In vivo mutation rate. J Virol 2000; 74(15): 7039-47.
[http://dx.doi.org/10.1128/JVI.74.15.7039-7047.2000] [PMID: 10888643]
[104]
Priet S, Sire J, Quérat G. Uracils as a cellular weapon against viruses and mechanisms of viral escape. Curr HIV Res 2006; 4(1): 31-42.
[http://dx.doi.org/10.2174/157016206775197673] [PMID: 16454709]
[105]
Klarmann GJ, Chen X, North TW, Preston BD. Incorporation of uracil into minus strand DNA affects the specificity of plus strand synthesis initiation during lentiviral reverse transcription. J Biol Chem 2003; 278(10): 7902-9.
[http://dx.doi.org/10.1074/jbc.M207223200] [PMID: 12458216]
[106]
Coffin JM, Hughes SH, Varmus HE, Eds. Retroviruses [Internet]. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 1997.[cited on: Jul 29 2019]. http://www.ncbi.nlm.nih.gov/books/NBK19376/
[107]
Kaiser SM, Emerman M. Uracil DNA glycosylase is dispensable for human immunodeficiency virus type 1 replication and does not contribute to the antiviral effects of the cytidine deaminase Apobec3G. J Virol 2006; 80(2): 875-82.
[http://dx.doi.org/10.1128/JVI.80.2.875-882.2006] [PMID: 16378989]
[108]
Chen R, Le Rouzic E, Kearney JA, Mansky LM, Benichou S. Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages. J Biol Chem 2004; 279(27): 28419-25.
[http://dx.doi.org/10.1074/jbc.M403875200] [PMID: 15096517]
[109]
Herate C, Vigne C, Guenzel CA, Lambele M, Rouyez M-C, Benichou S. Uracil DNA glycosylase interacts with the p32 subunit of the replication protein A complex to modulate HIV-1 reverse transcription for optimal virus dissemination. Retrovirology 2016; 13: 26.
[http://dx.doi.org/10.1186/s12977-016-0257-x] [PMID: 27068393]
[110]
Guenzel CA, Hérate C, Le Rouzic E, et al. Recruitment of the nuclear form of uracil DNA glycosylase into virus particles participates in the full infectivity of HIV-1. J Virol 2012; 86(5): 2533-44.
[http://dx.doi.org/10.1128/JVI.05163-11] [PMID: 22171270]
[111]
Priet S, Navarro J-M, Gros N, Querat G, Sire J. Functional role of HIV-1 virion-associated uracil DNA glycosylase 2 in the correction of G:U mispairs to G:C pairs. J Biol Chem 2003; 278(7): 4566-71.
[http://dx.doi.org/10.1074/jbc.M209311200] [PMID: 12458223]
[112]
Priet S, Gros N, Navarro J-M, et al. HIV-1-associated uracil DNA glycosylase activity controls dUTP misincorporation in viral DNA and is essential to the HIV-1 life cycle. Mol Cell 2005; 17(4): 479-90.
[http://dx.doi.org/10.1016/j.molcel.2005.01.016] [PMID: 15721252]
[113]
Chertova E, Chertov O, Coren LV, et al. Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages. J Virol 2006; 80(18): 9039-52.
[http://dx.doi.org/10.1128/JVI.01013-06] [PMID: 16940516]
[114]
Yang B, Chen K, Zhang C, Huang S, Zhang H. Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. J Biol Chem 2007; 282(16): 11667-75.
[http://dx.doi.org/10.1074/jbc.M606864200] [PMID: 17272283]
[115]
Wecker K, Morellet N, Bouaziz S, Roques BP. NMR structure of the HIV-1 regulatory protein Vpr in H2O/trifluoroethanol. Comparison with the Vpr N-terminal (1-51) and C-terminal (52-96) domains. Eur J Biochem 2002; 269(15): 3779-88.
[http://dx.doi.org/10.1046/j.1432-1033.2002.03067.x] [PMID: 12153575]
[116]
Morellet N, Bouaziz S, Petitjean P, Roques BP. NMR structure of the HIV-1 regulatory protein VPR. J Mol Biol 2003; 327(1): 215-27.
[http://dx.doi.org/10.1016/S0022-2836(03)00060-3] [PMID: 12614620]
[117]
Wen X, Casey Klockow L, Nekorchuk M, Sharifi HJ, de Noronha CMC. The HIV1 protein Vpr acts to enhance constitutive DCAF1-dependent UNG2 turnover. PLoS One 2012; 7(1)e30939
[http://dx.doi.org/10.1371/journal.pone.0030939] [PMID: 22292079]
[118]
Eldin P, Chazal N, Fenard D, Bernard E, Guichou J-F, Briant L. Vpr expression abolishes the capacity of HIV-1 infected cells to repair uracilated DNA. Nucleic Acids Res 2014; 42(3): 1698-710.
[http://dx.doi.org/10.1093/nar/gkt974] [PMID: 24178031]
[119]
Weil AF, Ghosh D, Zhou Y, et al. Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration. Proc Natl Acad Sci USA 2013; 110(6): E448-57.
[http://dx.doi.org/10.1073/pnas.1219702110] [PMID: 23341616]
[120]
Fenard D, Houzet L, Bernard E, et al. Uracil DNA Glycosylase 2 negatively regulates HIV-1 LTR transcription. Nucleic Acids Res 2009; 37(18): 6008-18.
[http://dx.doi.org/10.1093/nar/gkp673] [PMID: 19696076]
[121]
Hrecka K, Hao C, Shun M-C, Kaur S, Swanson SK, Florens L, et al. HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins. Proc Natl Acad Sci USA 2016; 113(27): E3921-30.
[122]
Morellet N, Roques BP, Bouaziz S. Structure-function relationship of Vpr: biological implications. Curr HIV Res 2009; 7(2): 184-210.
[http://dx.doi.org/10.2174/157016209787581490] [PMID: 19275588]
[123]
Shimura M, Onozuka Y, Yamaguchi T, Hatake K, Takaku F, Ishizaka Y. Micronuclei formation with chromosome breaks and gene amplification caused by Vpr, an accessory gene of human immunodeficiency virus. Cancer Res 1999; 59(10): 2259-64.
[PMID: 10344725]
[124]
Shimura M, Tanaka Y, Nakamura S, et al. Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1. FASEB J 1999; 13(6): 621-37.
[http://dx.doi.org/10.1096/fasebj.13.6.621] [PMID: 10094923]
[125]
Yan N, O’Day E, Wheeler LA, Engelman A, Lieberman J. HIV DNA is heavily uracilated, which protects it from autointegration. Proc Natl Acad Sci USA 2011; 108(22): 9244-9.
[http://dx.doi.org/10.1073/pnas.1102943108] [PMID: 21576478]
[126]
Schröfelbauer B, Hakata Y, Landau NR. HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. Proc Natl Acad Sci USA 2007; 104(10): 4130-5.
[http://dx.doi.org/10.1073/pnas.0610167104] [PMID: 17360488]
[127]
Wang Z, Mosbaugh DW. Uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 encodes a binding protein specific for uracil-DNA glycosylase. J Biol Chem 1989; 264(2): 1163-71.
[PMID: 2492016]
[128]
Cone R, Bonura T, Friedberg EC. Inhibitor of uracil-DNA glycosylase induced by bacteriophage PBS2. Purification and preliminary characterization. J Biol Chem 1980; 255(21): 10354-8.
[PMID: 6776115]
[129]
Assefa NG, Niiranen L, Johnson KA, et al. Structural and biophysical analysis of interactions between cod and human uracil-DNA N-glycosylase (UNG) and UNG inhibitor (Ugi). Acta Crystallogr D Biol Crystallogr 2014; 70(Pt 8): 2093-100.
[http://dx.doi.org/10.1107/S1399004714011699] [PMID: 25084329]
[130]
Studebaker AW, Ariza ME, Williams MV. Depletion of uracil-DNA glycosylase activity is associated with decreased cell proliferation. Biochem Biophys Res Commun 2005; 334(2): 509-15.
[http://dx.doi.org/10.1016/j.bbrc.2005.06.118] [PMID: 16005850]
[131]
Serrano-Heras G, Ruiz-Masó JA, del Solar G, Espinosa M, Bravo A, Salas M. Protein p56 from the Bacillus subtilis phage phi29 inhibits DNA-binding ability of uracil-DNA glycosylase. Nucleic Acids Res 2007; 35(16): 5393-401.
[http://dx.doi.org/10.1093/nar/gkm584] [PMID: 17698500]
[132]
Asensio JL, Pérez-Lago L, Lázaro JM, González C, Serrano-Heras G, Salas M. Novel dimeric structure of phage φ29-encoded protein p56: insights into uracil-DNA glycosylase inhibition. Nucleic Acids Res 2011; 39(22): 9779-88.
[http://dx.doi.org/10.1093/nar/gkr667] [PMID: 21890898]
[133]
Baños-Sanz JI, Mojardín L, Sanz-Aparicio J, et al. Crystal structure and functional insights into uracil-DNA glycosylase inhibition by phage Φ29 DNA mimic protein p56. Nucleic Acids Res 2013; 41(13): 6761-73.
[http://dx.doi.org/10.1093/nar/gkt395] [PMID: 23671337]
[134]
Wang H-C, Hsu K-C, Yang J-M, et al. Staphylococcus aureus protein SAUGI acts as a uracil-DNA glycosylase inhibitor. Nucleic Acids Res 2014; 42(2): 1354-64.
[http://dx.doi.org/10.1093/nar/gkt964] [PMID: 24150946]
[135]
Caradonna SJ, Cheng YC. Uracil DNA-glycosylase. Purification and properties of this enzyme isolated from blast cells of acute myelocytic leukemia patients. J Biol Chem 1980; 255(6): 2293-300.
[PMID: 6766936]
[136]
Krokan H, Wittwer CU. Uracil DNa-glycosylase from HeLa cells: general properties, substrate specificity and effect of uracil analogs. Nucleic Acids Res 1981; 9(11): 2599-613.
[http://dx.doi.org/10.1093/nar/9.11.2599] [PMID: 7279657]
[137]
Seal G, Arenaz P, Sirover MA. Purification and properties of the human placental uracil DNA glycosylase. Biochim Biophys Acta 1987; 925(2): 226-33.
[http://dx.doi.org/10.1016/0304-4165(87)90113-9] [PMID: 3620497]
[138]
Jiang YL, Ichikawa Y, Stivers JT. Inhibition of uracil DNA glycosylase by an oxacarbenium ion mimic. Biochemistry 2002; 41(22): 7116-24.
[http://dx.doi.org/10.1021/bi025694y] [PMID: 12033946]
[139]
Jiang YL, Krosky DJ, Seiple L, Stivers JT. Uracil-directed ligand tethering: an efficient strategy for uracil DNA glycosylase (UNG) inhibitor development. J Am Chem Soc 2005; 127(49): 17412-20.
[http://dx.doi.org/10.1021/ja055846n] [PMID: 16332091]

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