The flexible loop of the human cytomegalovirus DNA polymerase processivity factor ppUL44 is required for efficient DNA binding and replication in cells

Journal of Virology

Volumn 83, Issue 18, 2009, Pages 9567-9576

  Alvisi, Gualtiero ^a,b,g   Roth, Daniela Martino ^b   Camozzi, Daria ^a   Pari, Gregory S ^c   Loregian, Arianna ^d   Ripalti, Alessandro ^e   Jans, David A ^b,f  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b MONASH UNIVERSITY   (Australia)

^c UNIVERSITY OF NEVADA SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF PADOVA   (Italy)

^e UNIVERSITY OF BOLOGNA   (Italy)

^f Australian Government Australian Research Council   (Australia)

^g UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DEOXYRIBONUCLEASE; DETERGENT; DNA POLYMERASE; DOUBLE STRANDED DNA; HETERODIMER; MUTANT PROTEIN; PROPOSED PROCESSIVITY UL44 PROTEIN; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING SITE; CELL FRACTIONATION; CELL NUCLEUS; CONTROLLED STUDY; DIMERIZATION; DNA BINDING; DNA REPLICATION; DNA STRUCTURE; EMBRYO; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; VIRUS GENE; VIRUS INHIBITION; VIRUS REPLICATION; WILD TYPE;

BINDING SITES; CELL LINE; CYTOMEGALOVIRUS; DNA; DNA REPLICATION; DNA-BINDING PROTEINS; DNA-DIRECTED DNA POLYMERASE; HUMANS; PHOSPHOPROTEINS; PROTEIN CONFORMATION; VIRAL PROTEINS;

HUMAN HERPESVIRUS 5;

EID: 69449102907     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.00669-09     Document Type: Article

References (46)

1. Agulnick, A. D., J. R. Thompson, S. Iyengar, G. Pearson, D. Ablashi, and R. P. Ricciardi. 1993. Identification of a DNA-binding protein of human herpesvirus 6, a putative DNA polymerase stimulatory factor. J. Gen. Virol. 74(Pt. 6):1003-1009.
2. Allan, J., T. Mitchell, N. Harborne, L. Bohm, and C. Crane-Robinson. 1986. Roles of H1 domains in determining higher order chromatin structure and H1 location. J. Mol. Biol. 187:591-601.
3. Alvisi, G., S. Avanzi, D. Musiani, D. Camozzi, V. Leoni, J. D. Ly-Huynh, and A. Ripalti. 2008. Nuclear import of HSV-1 DNA polymerase processivity factor UL42 is mediated by a C-terminally located bipartite nuclear localization signal. Biochemistry 47:13764-13777.
4. Alvisi, G., D. A. Jans, J. Guo, L. A. Pinna, and A. Ripalti. 2005. A protein kinase CK2 site flanking the nuclear targeting signal enhances nuclear transport of human cytomegalovirus ppUL44. Traffic 6:1002-1013. (Pubitemid 41472459)
5. Alvisi, G., D. A. Jans, and A. Ripalti. 2006. Human cytomegalovirus (HCMV) DNA polymerase processivity factor ppUL44 dimerizes in the cytosol before translocation to the nucleus. Biochemistry 45:6866-6872. (Pubitemid 43856672)
6. Alvisi, G., S. M. Rawlinson, R. Ghildyal, A. Ripalti, and D. A. Jans. 2008. Regulated nucleocytoplasmic trafficking of viral gene products: a therapeutic target? Biochim. Biophys. Acta 1784:213-227.
7. Alvisi, G., A. Ripalti, A. Ngankeu, M. Giannandrea, S. G. Caraffi, M. M. Dias, and D. A. Jans. 2006. Human cytomegalovirus DNA polymerase catalytic subunit pUL54 possesses independently acting nuclear localization and ppUL44 binding motifs. Traffic 7:1322-1332. (Pubitemid 44364171)
8. Anders, D. G., M. A. Kacica, G. Pari, and S. M. Punturieri. 1992. Boundaries and structure of human cytomegalovirus oriLyt, a complex origin for lytic-phase DNA replication. J. Virol. 66:3373-3384.
9. Appleton, B. A., J. Brooks, A. Loregian, D. J. Filman, D. M. Coen, and J. M. Hogle. 2006. Crystal structure of the cytomegalovirus DNA polymerase subunit UL44 in complex with the C terminus from the catalytic subunit. Differences in structure and function relative to unliganded UL44. J. Biol. Chem. 281:5224-5232.
10. Appleton, B. A., A. Loregian, D. J. Filman, D. M. Coen, and J. M. Hogle. 2004. The cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer. Mol. Cell 15:233-244.
11. Axelrod, D., P. Ravdin, D. E. Koppel, J. Schlessinger, W. W. Webb, E. L. Elson, and T. R. Podleski. 1976. Lateral motion of fluorescently labeled acetylcholine receptors in membranes of developing muscle fibers. Proc. Natl. Acad. Sci. USA 73:4594-4598.
12. Bauerle, M., D. Doenecke, and W. Albig. 2002. The requirement of H1 histones for a heterodimeric nuclear import receptor. J. Biol. Chem. 277: 32480-32489.
13. Chen, Y., C. M. Livingston, S. D. Carrington-Lawrence, P. Bai, and S. K. Weller. 2007. A mutation in the human herpes simplex virus type 1 UL52 zinc finger motif results in defective primase activity but can recruit viral polymerase and support viral replication efficiently. J. Virol. 81:8742-8751. (Pubitemid 47242847)
14. Ertl, P. F., and K. L. Powell. 1992. Physical and functional interaction of human cytomegalovirus DNA polymerase and its accessory protein (ICP36) expressed in insect cells. J. Virol. 66:4126-4133.
15. Gao, Y., K. Colletti, and G. S. Pari. 2008. Identification of human cytomegalovirus UL84 virus- and cell-encoded binding partners by using proteomics analysis. J. Virol. 82:96-104. (Pubitemid 350309127)
16. Gerlitz, G., I. Livnat, C. Ziv, O. Yarden, M. Bustin, and O. Reiner. 2007. Migration cues induce chromatin alterations. Traffic 8:1521-1529. (Pubitemid 47578358)
17. Hope, T. J., N. P. Klein, M. E. Elder, and T. G. Parslow. 1992. transdominant inhibition of human immunodeficiency virus type 1 Rev occurs through formation of inactive protein complexes. J. Virol. 66:1849-1855.
18. Hubner, S., J. E. Eam, K. M. Wagstaff, and D. A. Jans. 2006. Quantitative analysis of localization and nuclear aggregate formation induced by GFP-lamin A mutant proteins in living HeLa cells. J. Cell Biochem. 98:810-826. (Pubitemid 43993398)
19. Jiang, C., Y. T. Hwang, J. C. Randell, D. M. Coen, and C. B. Hwang. 2007. Mutations that decrease DNA binding of the processivity factor of the herpes simplex virus DNA polymerase reduce viral yield, alter the kinetics of viral DNA replication, and decrease the fidelity of DNA replication. J. Virol. 81:3495-3502. (Pubitemid 46456658)
20. Jiang, C., Y. T. Hwang, G. Wang, J. C. Randell, D. M. Coen, and C. B. Hwang. 2007. Herpes simplex virus mutants with multiple substitutions affecting DNA binding of UL42 are impaired for viral replication and DNA synthesis. J. Virol. 81:12077-12079. (Pubitemid 47623839)
21. Jiang, C., G. Komazin-Meredith, W. Tian, D. M. Coen, and C. B. Hwang. 2009. Mutations that increase DNA binding by the processivity factor of herpes simplex virus affect virus production and DNA replication fidelity. J. Virol. 83:7573-7580.
22. Komazin-Meredith, G., R. J. Petrella, W. L. Santos, D. J. Filman, J. M. Hogle, G. L. Verdine, M. Karplus, and D. M. Coen. 2008. The human cytomegalovirus UL44 C clamp wraps around DNA. Structure 16:1214-1225.
23. Komazin-Meredith, G., W. L. Santos, D. J. Filman, J. M. Hogle, G. L. Verdine, and D. M. Coen. 2008. The positively charged surface of herpes simplex virus UL42 mediates DNA binding. J. Biol. Chem. 283:6154-6161.
24. Lang, I., M. Scholz, and R. Peters. 1986. Molecular mobility and nucleocytoplasmic flux in hepatoma cells. J. Cell Biol. 102:1183-1190. (Pubitemid 16038061)
25. Loh, L. C., V. D. Keeler, and J. D. Shanley. 1999. Sequence requirements for the nuclear localization of the murine cytomegalovirus M44 gene product pp50. Virology 259:43-59.
26. Loregian, A., B. A. Appleton, J. M. Hogle, and D. M. Coen. 2004. Residues of human cytomegalovirus DNA polymerase catalytic subunit UL54 that are necessary and sufficient for interaction with the accessory protein UL44. J. Virol. 78:158-167. (Pubitemid 37549728)
27. Loregian, A., B. A. Appleton, J. M. Hogle, and D. M. Coen. 2004. Specific residues in the connector loop of the human cytomegalovirus DNA polymerase accessory protein UL44 are crucial for interaction with the UL54 catalytic subunit. J. Virol. 78:9084-9092. (Pubitemid 39096519)
28. Malm, G., and M. L. Engman. 2007. Congenital cytomegalovirus infections. Semin. Fetal Neonatal Med. 12:154-159.
29. Marschall, M., M. Freitag, P. Suchy, D. Romaker, R. Kupfer, M. Hanke, and T. Stamminger. 2003. The protein kinase pUL97 of human cytomegalovirus interacts with and phosphorylates the DNA polymerase processivity factor pUL44. Virology 311:60-71. (Pubitemid 36794210)
30. Mocarski, E. S., L. Pereira, and N. Michael. 1985. Precise localization of genes on large animal virus genomes: use of lambda gt11 and monoclonal antibodies to map the gene for a cytomegalovirus protein family. Proc. Natl. Acad. Sci. USA 82:1266-1270.
31. Orrego, M., I. Ponte, A. Roque, N. Buschati, X. Mora, and P. Suau. 2007. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin. BMC Biol. 5:22. (Pubitemid 46938712)
32. Pari, G. S., and D. G. Anders. 1993. Eleven loci encoding trans-acting factors are required for transient complementation of human cytomegalovirus ori-Lyt-dependent DNA replication. J. Virol. 67:6979-6988.
33. Pari, G. S., M. A. Kacica, and D. G. Anders. 1993. Open reading frames UL44, IRS1/TRS1, and UL36-38 are required for transient complementation of human cytomegalovirus oriLyt-dependent DNA synthesis. J. Virol. 67:2575-2582.
34. Partikian, A., B. Olveczky, R. Swaminathan, Y. Li, and A. S. Verkman. 1998. Rapid diffusion of green fluorescent protein in the mitochondrial matrix. J. Cell Biol. 140:821-829. (Pubitemid 28141220)
35. Pettersen, E. F., T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, and T. E. Ferrin. 2004. UCSF Chimera: a visualization system for exploratory research and analysis. J. Comput. Chem. 25:1605-1612.
36. Poon, I. K., C. Oro, M. M. Dias, J. Zhang, and D. A. Jans. 2005. Apoptin nuclear accumulation is modulated by a CRM1-recognized nuclear export signal that is active in normal but not in tumor cells. Cancer Res. 65:7059-7064.
37. Prichard, M. N., H. Lawlor, G. M. Duke, C. Mo, Z. Wang, M. Dixon, G. Kemble, and E. R. Kern. 2005. Human cytomegalovirus uracil DNA glycosylase associates with ppUL44 and accelerates the accumulation of viral DNA. Virol. J. 2:55.
38. Randell, J. C., G. Komazin, C. Jiang, C. B. Hwang, and D. M. Coen. 2005. Effects of substitutions of arginine residues on the basic surface of herpes simplex virus UL42 support a role for DNA binding in processive DNA synthesis. J. Virol. 79:12025-12034.
39. Ripalti, A., M. C. Boccuni, F. Campanini, and M. P. Landini. 1995. Cytomegalovirus- mediated induction of antisense mRNA expression to UL44 inhibits virus replication in an astrocytoma cell line: identification of an essential gene. J. Virol. 69:2047-2057.
40. Roth, D. M., I. Harper, C. W. Pouton, and D. A. Jans. Modulation of nucleocytoplasmic trafficking by retention in cytoplasm or nucleus. J. Cell Biochem., in press.
41. Sinigalia, E., G. Alvisi, B. Mercorelli, D. M. Coen, G. S. Pari, D. A. Jans, A. Ripalti, G. Palu, and A. Loregian. 2008. Role of homodimerization of human cytomegalovirus DNA polymerase accessory protein UL44 in origin-dependent DNA replication in cells. J. Virol. 82:12574-12579.
42. Steininger, C. 2007. Clinical relevance of cytomegalovirus infection in patients with disorders of the immune system. Clin. Microbiol. Infect. 13:953-963.
43. Strang, B. L., E. Sinigalia, L. A. Silva, D. M. Coen, and A. Loregian. 2009. Analysis of the association of the human cytomegalovirus DNA polymerase subunit UL44 with the viral DNA replication factor UL84. J. Virol. 83:7581-7589.
44. Takeda, K., M. Haque, E. Nagoshi, M. Takemoto, T. Shimamoto, Y. Yoneda, and K. Yamanishi. 2000. Characterization of human herpesvirus 7 U27 gene product and identification of its nuclear localization signal. Virology 272: 394-401. (Pubitemid 30480199)
45. Weiland, K. L., N. L. Oien, F. Homa, and M. W. Wathen. 1994. Functional analysis of human cytomegalovirus polymerase accessory protein. Virus Res. 34:191-206.
46. Zuccola, H. J., D. J. Filman, D. M. Coen, and J. M. Hogle. 2000. The crystal structure of an unusual processivity factor, herpes simplex virus UL42, bound to the C terminus of its cognate polymerase. Mol. Cell 5:267-278.