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. 1998 Mar 1;26(5):1240–1247. doi: 10.1093/nar/26.5.1240

Adenovirus DNA polymerase: domain organisation and interaction with preterminal protein.

E J Parker 1, C H Botting 1, A Webster 1, R T Hay 1
PMCID: PMC147410  PMID: 9469832

Abstract

Adenovirus DNA polymerase is one of three viral proteins and two cellular proteins required for replication of the adenovirus genome. During initiation of viral DNA synthesis the viral DNA polymerase transfers dCMP onto the adenovirus preterminal protein, to which it is tightly bound. The domain structure of the 140 kDa DNA polymerase has been probed by partial proteolysis and the sites of proteolytic cleavage determined by N-terminal sequencing. At least four domains can be recognised within the DNA polymerase. Adenovirus preterminal protein interacts with three of the four proteolytically derived domains. This was confirmed by cloning and expression of each of the individual domains. These data indicate that, like other members of the pol alpha family of DNA polymerases, the adenovirus DNA polymerase has a multidomain structure and that interaction with preterminal protein takes place with non-contiguous regions of the polypeptide chain over a large surface area of the viral DNA polymerase.

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Selected References

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  1. Armentero M. T., Horwitz M., Mermod N. Targeting of DNA polymerase to the adenovirus origin of DNA replication by interaction with nuclear factor I. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11537–11541. doi: 10.1073/pnas.91.24.11537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett K. L., Pearson G. D. Sequence conversion during postreplicative adenovirus overlap recombination. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1397–1401. doi: 10.1073/pnas.90.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernad A., Blanco L., Lázaro J. M., Martín G., Salas M. A conserved 3'----5' exonuclease active site in prokaryotic and eukaryotic DNA polymerases. Cell. 1989 Oct 6;59(1):219–228. doi: 10.1016/0092-8674(89)90883-0. [DOI] [PubMed] [Google Scholar]
  4. Bosher J., Robinson E. C., Hay R. T. Interactions between the adenovirus type 2 DNA polymerase and the DNA binding domain of nuclear factor I. New Biol. 1990 Dec;2(12):1083–1090. [PubMed] [Google Scholar]
  5. Chen M., Horwitz M. S. Dissection of functional domains of adenovirus DNA polymerase by linker-insertion mutagenesis. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6116–6120. doi: 10.1073/pnas.86.16.6116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen M., Mermod N., Horwitz M. S. Protein-protein interactions between adenovirus DNA polymerase and nuclear factor I mediate formation of the DNA replication preinitiation complex. J Biol Chem. 1990 Oct 25;265(30):18634–18642. [PubMed] [Google Scholar]
  7. Cleat P. H., Hay R. T. Co-operative interactions between NFI and the adenovirus DNA binding protein at the adenovirus origin of replication. EMBO J. 1989 Jun;8(6):1841–1848. doi: 10.1002/j.1460-2075.1989.tb03579.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coenjaerts F. E., van Oosterhout J. A., van der Vliet P. C. The Oct-1 POU domain stimulates adenovirus DNA replication by a direct interaction between the viral precursor terminal protein-DNA polymerase complex and the POU homeodomain. EMBO J. 1994 Nov 15;13(22):5401–5409. doi: 10.1002/j.1460-2075.1994.tb06875.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coenjaerts F. E., van der Vliet P. C. Early dissociation of nuclear factor I from the origin during initiation of adenovirus DNA replication studied by origin immobilization. Nucleic Acids Res. 1994 Dec 11;22(24):5235–5240. doi: 10.1093/nar/22.24.5235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dekker J., Kanellopoulos P. N., Loonstra A. K., van Oosterhout J. A., Leonard K., Tucker P. A., van der Vliet P. C. Multimerization of the adenovirus DNA-binding protein is the driving force for ATP-independent DNA unwinding during strand displacement synthesis. EMBO J. 1997 Mar 17;16(6):1455–1463. doi: 10.1093/emboj/16.6.1455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dekker N., Cox M., Boelens R., Verrijzer C. P., van der Vliet P. C., Kaptein R. Solution structure of the POU-specific DNA-binding domain of Oct-1. Nature. 1993 Apr 29;362(6423):852–855. doi: 10.1038/362852a0. [DOI] [PubMed] [Google Scholar]
  12. Earl P. L., Jones E. V., Moss B. Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3659–3663. doi: 10.1073/pnas.83.11.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fredman J. N., Engler J. A. Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro. J Virol. 1993 Jun;67(6):3384–3395. doi: 10.1128/jvi.67.6.3384-3395.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gibbs J. S., Chiou H. C., Hall J. D., Mount D. W., Retondo M. J., Weller S. K., Coen D. M. Sequence and mapping analyses of the herpes simplex virus DNA polymerase gene predict a C-terminal substrate binding domain. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7969–7973. doi: 10.1073/pnas.82.23.7969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hanke T., Szawlowski P., Randall R. E. Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen. J Gen Virol. 1992 Mar;73(Pt 3):653–660. doi: 10.1099/0022-1317-73-3-653. [DOI] [PubMed] [Google Scholar]
  16. Hay R. T., Stow N. D., McDougall I. M. Replication of adenovirus mini-chromosomes. J Mol Biol. 1984 Jun 5;175(4):493–510. doi: 10.1016/0022-2836(84)90181-5. [DOI] [PubMed] [Google Scholar]
  17. Joung I., Engler J. A. Mutations in two cysteine-histidine-rich clusters in adenovirus type 2 DNA polymerase affect DNA binding. J Virol. 1992 Oct;66(10):5788–5796. doi: 10.1128/jvi.66.10.5788-5796.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Joung I., Horwitz M. S., Engler J. A. Mutagenesis of conserved region I in the DNA polymerase from human adenovirus serotype 2. Virology. 1991 Sep;184(1):235–241. doi: 10.1016/0042-6822(91)90840-8. [DOI] [PubMed] [Google Scholar]
  19. Joyce C. M., Steitz T. A. Function and structure relationships in DNA polymerases. Annu Rev Biochem. 1994;63:777–822. doi: 10.1146/annurev.bi.63.070194.004021. [DOI] [PubMed] [Google Scholar]
  20. King A. J., van der Vliet P. C. A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism. EMBO J. 1994 Dec 1;13(23):5786–5792. doi: 10.1002/j.1460-2075.1994.tb06917.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Larder B. A., Kemp S. D., Darby G. Related functional domains in virus DNA polymerases. EMBO J. 1987 Jan;6(1):169–175. doi: 10.1002/j.1460-2075.1987.tb04735.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lindenbaum J. O., Field J., Hurwitz J. The adenovirus DNA binding protein and adenovirus DNA polymerase interact to catalyze elongation of primed DNA templates. J Biol Chem. 1986 Aug 5;261(22):10218–10227. [PubMed] [Google Scholar]
  23. Monaghan A., Hay R. T. Pyridoxal 5'-phosphate inhibition of adenovirus DNA polymerase. J Biol Chem. 1996 Sep 27;271(39):24242–24248. doi: 10.1074/jbc.271.39.24242. [DOI] [PubMed] [Google Scholar]
  24. Monaghan A., Webster A., Hay R. T. Adenovirus DNA binding protein: helix destabilising properties. Nucleic Acids Res. 1994 Mar 11;22(5):742–748. doi: 10.1093/nar/22.5.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mul Y. M., Van der Vliet P. C. Nuclear factor I enhances adenovirus DNA replication by increasing the stability of a preinitiation complex. EMBO J. 1992 Feb;11(2):751–760. doi: 10.1002/j.1460-2075.1992.tb05108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mul Y. M., van der Vliet P. C. The adenovirus DNA binding protein effects the kinetics of DNA replication by a mechanism distinct from NFI or Oct-1. Nucleic Acids Res. 1993 Feb 11;21(3):641–647. doi: 10.1093/nar/21.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mul Y. M., van der Vliet P. C. The adenovirus DNA binding protein effects the kinetics of DNA replication by a mechanism distinct from NFI or Oct-1. Nucleic Acids Res. 1993 Feb 11;21(3):641–647. doi: 10.1093/nar/21.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Méndez J., Blanco L., Esteban J. A., Bernad A., Salas M. Initiation of phi 29 DNA replication occurs at the second 3' nucleotide of the linear template: a sliding-back mechanism for protein-primed DNA replication. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9579–9583. doi: 10.1073/pnas.89.20.9579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nagata K., Guggenheimer R. A., Hurwitz J. Adenovirus DNA replication in vitro: synthesis of full-length DNA with purified proteins. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4266–4270. doi: 10.1073/pnas.80.14.4266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pronk R., Van Driel W., Van der Vliet P. C. Replication of adenovirus DNA in vitro is ATP-independent. FEBS Lett. 1994 Jan 3;337(1):33–38. doi: 10.1016/0014-5793(94)80624-1. [DOI] [PubMed] [Google Scholar]
  31. Pronk R., van der Vliet P. C. The adenovirus terminal protein influences binding of replication proteins and changes the origin structure. Nucleic Acids Res. 1993 May 25;21(10):2293–2300. doi: 10.1093/nar/21.10.2293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pruijn G. J., van Driel W., van der Vliet P. C. Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication. Nature. 1986 Aug 14;322(6080):656–659. doi: 10.1038/322656a0. [DOI] [PubMed] [Google Scholar]
  33. Roovers D. J., Overman P. F., Chen X. Q., Sussenbach J. S. Linker mutation scanning of the genes encoding the adenovirus type 5 terminal protein precursor and DNA polymerase. Virology. 1991 Jan;180(1):273–284. doi: 10.1016/0042-6822(91)90032-7. [DOI] [PubMed] [Google Scholar]
  34. Roovers D. J., van der Lee F. M., van der Wees J., Sussenbach J. S. Analysis of the adenovirus type 5 terminal protein precursor and DNA polymerase by linker insertion mutagenesis. J Virol. 1993 Jan;67(1):265–276. doi: 10.1128/jvi.67.1.265-276.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schaack J., Ho W. Y., Freimuth P., Shenk T. Adenovirus terminal protein mediates both nuclear matrix association and efficient transcription of adenovirus DNA. Genes Dev. 1990 Jul;4(7):1197–1208. doi: 10.1101/gad.4.7.1197. [DOI] [PubMed] [Google Scholar]
  36. Smart J. E., Stillman B. W. Adenovirus terminal protein precursor. Partial amino acid sequence and the site of covalent linkage to virus DNA. J Biol Chem. 1982 Nov 25;257(22):13499–13506. [PubMed] [Google Scholar]
  37. Stow N. D. The infectivity of adenovirus genomes lacking DNA sequences from their left-hand termini. Nucleic Acids Res. 1982 Sep 11;10(17):5105–5119. doi: 10.1093/nar/10.17.5105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stuiver M. H., van der Vliet P. C. Adenovirus DNA-binding protein forms a multimeric protein complex with double-stranded DNA and enhances binding of nuclear factor I. J Virol. 1990 Jan;64(1):379–386. doi: 10.1128/jvi.64.1.379-386.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Temperley S. M., Hay R. T. Recognition of the adenovirus type 2 origin of DNA replication by the virally encoded DNA polymerase and preterminal proteins. EMBO J. 1992 Feb;11(2):761–768. doi: 10.1002/j.1460-2075.1992.tb05109.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Temperley S. M., Hay R. T. Replication of adenovirus type 4 DNA by a purified fraction from infected cells. Nucleic Acids Res. 1991 Jun 25;19(12):3243–3249. doi: 10.1093/nar/19.12.3243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tucker P. A., Tsernoglou D., Tucker A. D., Coenjaerts F. E., Leenders H., van der Vliet P. C. Crystal structure of the adenovirus DNA binding protein reveals a hook-on model for cooperative DNA binding. EMBO J. 1994 Jul 1;13(13):2994–3002. doi: 10.1002/j.1460-2075.1994.tb06598.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wang J., Sattar A. K., Wang C. C., Karam J. D., Konigsberg W. H., Steitz T. A. Crystal structure of a pol alpha family replication DNA polymerase from bacteriophage RB69. Cell. 1997 Jun 27;89(7):1087–1099. doi: 10.1016/s0092-8674(00)80296-2. [DOI] [PubMed] [Google Scholar]
  43. Watson C. J., Hay R. T. Expression of adenovirus type 2 DNA polymerase in insect cells infected with a recombinant baculovirus. Nucleic Acids Res. 1990 Mar 11;18(5):1167–1173. doi: 10.1093/nar/18.5.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Webster A., Leith I. R., Hay R. T. Activation of adenovirus-coded protease and processing of preterminal protein. J Virol. 1994 Nov;68(11):7292–7300. doi: 10.1128/jvi.68.11.7292-7300.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Webster A., Leith I. R., Hay R. T. Domain organization of the adenovirus preterminal protein. J Virol. 1997 Jan;71(1):539–547. doi: 10.1128/jvi.71.1.539-547.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Webster A., Leith I. R., Nicholson J., Hounsell J., Hay R. T. Role of preterminal protein processing in adenovirus replication. J Virol. 1997 Sep;71(9):6381–6389. doi: 10.1128/jvi.71.9.6381-6389.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wong S. W., Wahl A. F., Yuan P. M., Arai N., Pearson B. E., Arai K., Korn D., Hunkapiller M. W., Wang T. S. Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 1988 Jan;7(1):37–47. doi: 10.1002/j.1460-2075.1988.tb02781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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