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. 1979 Jul 25;6(10):3369–3386. doi: 10.1093/nar/6.10.3369

The effect of aphidicolin on adenovirus DNA synthesis.

M Longiaru, J E Ikeda, Z Jarkovsky, S B Horwitz, M S Horwitz
PMCID: PMC327939  PMID: 482131

Abstract

Aphidicolin inhibits adenovirus DNA replication in HeLa cells and in a cell-free, infected, nuclear extract in which viral DNA is elongated. The compound inhibits alpha DNA polymerase, extensively purified from HeLa cells, but has little or no effect on the beta or gamma DNA polymerases similarly purified. Aphidicolin does not affect thymidine uptake by cells nor does synthesis as it also inhibits DNA replication in uninfected cells. The inhibition by aphidicolin is reversible if the drug is removed within 18 hrs after addition to HeLa or Chinese Hamster Ovary cells but the cells are irreversibly affected if the drug remains for 48 hours.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abboud M. M., Horwitz M. S. The DNA polymerases associated with the adenovirus type 2 replication complex: effect of 2'-3'-dideoxythymidine-5'-triphosphate on viral DNA synthesis. Nucleic Acids Res. 1979 Mar;6(3):1025–1039. doi: 10.1093/nar/6.3.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arens M., Yamashita T., Padmanabhan R., Tsuruo T., Green M. Adenovirus deoxyribonucleic acid replication. Characterization of the enzyme activities of a soluble replication system. J Biol Chem. 1977 Nov 25;252(22):7947–7954. [PubMed] [Google Scholar]
  3. BESSMAN M. J., LEHMAN I. R., SIMMS E. S., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. II. General properties of the reaction. J Biol Chem. 1958 Jul;233(1):171–177. [PubMed] [Google Scholar]
  4. Brison O., Kedinger C., Wilhelm J. Enzymatic properties of viral replication complexes isolated from adenovirus type 2-infected HeLa cell nuclei. J Virol. 1977 Nov;24(2):423–435. doi: 10.1128/jvi.24.2.423-435.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bucknall R. A., Moores H., Simms R., Hesp B. Antiviral effects of aphidicolin, a new antibiotic produced by Cephalosporium aphidicola. Antimicrob Agents Chemother. 1973 Sep;4(3):294–298. doi: 10.1128/aac.4.3.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang L. M., Bollum F. J. Variation of deoxyribonucleic acid polymerase activities during rat liver regeneration. J Biol Chem. 1972 Dec 25;247(24):7948–7950. [PubMed] [Google Scholar]
  7. Chang L. M., Brown M., Bollum F. J. Induction of DNA polymerase in mouse L cells. J Mol Biol. 1973 Feb 15;74(1):1–8. doi: 10.1016/0022-2836(73)90349-5. [DOI] [PubMed] [Google Scholar]
  8. Chiu R. W., Baril E. F. Nuclear DNA polymerases and the HeLa cell cycle. J Biol Chem. 1975 Oct 10;250(19):7951–7957. [PubMed] [Google Scholar]
  9. Edenberg H. J., Anderson S., DePamphilis M. L. Involvement of DNA polymerase alpha in simian virus 40 DNA replication. J Biol Chem. 1978 May 10;253(9):3273–3280. [PubMed] [Google Scholar]
  10. Frenkel G. D. Adenovirus DNA synthesis in vitro in an isolated complex. J Virol. 1978 Jan;25(1):459–463. doi: 10.1128/jvi.25.1.459-463.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heil A., Zillig W. Reconstitution of bacterial DNA-dependent RNA-polymerase from isolated subunits as a tool for the elucidation of the role of the subunits in transcription. FEBS Lett. 1970 Dec;11(3):165–168. doi: 10.1016/0014-5793(70)80519-1. [DOI] [PubMed] [Google Scholar]
  12. Horwitz M. S., Horwitz S. B. Intracellular degradation of HeLa and adenovirus type 2 DNA induced by camptothecin. Biochem Biophys Res Commun. 1971 Nov 5;45(3):723–727. doi: 10.1016/0006-291x(71)90476-1. [DOI] [PubMed] [Google Scholar]
  13. Horwitz M. S. Intermediates in the synthesis of type 2 adenovirus deoxyribonucleic acid. J Virol. 1971 Nov;8(5):675–683. doi: 10.1128/jvi.8.5.675-683.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Horwitz S. B., Chang C. K., Grollman A. P. Studies on camptothecin. I. Effects of nucleic acid and protein synthesis. Mol Pharmacol. 1971 Nov;7(6):632–644. [PubMed] [Google Scholar]
  15. Ikegami S., Taguchi T., Ohashi M., Oguro M., Nagano H., Mano Y. Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-alpha. Nature. 1978 Oct 5;275(5679):458–460. doi: 10.1038/275458a0. [DOI] [PubMed] [Google Scholar]
  16. Ito K., Arens M., Green M. Isolation of DNA polymerase gamma from an adenovirus 2 DNA replication complex. J Virol. 1975 Jun;15(6):1507–1510. doi: 10.1128/jvi.15.6.1507-1510.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaplan L. M., Kelinman R. E., Horwitz M. S. Replication of adenovirus type 2 DNA in vitro. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4425–4429. doi: 10.1073/pnas.74.10.4425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lechner R. L., Kelly T. J., Jr The structure of replicating adenovirus 2 DNA molecules. Cell. 1977 Dec;12(4):1007–1020. doi: 10.1016/0092-8674(77)90165-9. [DOI] [PubMed] [Google Scholar]
  19. Loike J. D., Horwitz S. B. Effects of podophyllotoxin and VP-16-213 on microtubule assembly in vitro and nucleoside transport in HeLa cells. Biochemistry. 1976 Dec 14;15(25):5435–5443. doi: 10.1021/bi00670a003. [DOI] [PubMed] [Google Scholar]
  20. Maizel J. V., Jr, White D. O., Scharff M. D. The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7A, and 12. Virology. 1968 Sep;36(1):115–125. doi: 10.1016/0042-6822(68)90121-9. [DOI] [PubMed] [Google Scholar]
  21. Matsukage A., Sivarajan M., Wilson S. H. Studies on DNA alpha-polymerase of mouse myeloma: partial purification and comparison of three molecular forms of the enzyme. Biochemistry. 1976 Nov 30;15(24):5305–5314. doi: 10.1021/bi00669a017. [DOI] [PubMed] [Google Scholar]
  22. Ohashi M., Taguchi T., Ikegami S. Aphidicolin: a specific inhibitor of DNA polymerases in the cytosol of rat liver. Biochem Biophys Res Commun. 1978 Jun 29;82(4):1084–1090. doi: 10.1016/0006-291x(78)90298-x. [DOI] [PubMed] [Google Scholar]
  23. Spadari S., Weissbach A. The interrelation between DNA synthesis and various DNA polymerase activities in synchronized HeLa cells. J Mol Biol. 1974 Jun 15;86(1):11–20. doi: 10.1016/s0022-2836(74)80003-3. [DOI] [PubMed] [Google Scholar]
  24. Waqar M. A., Evans M. J., Huberman J. A. Effect of 2',3'-dideoxythymidine-5'-triphosphate on HeLa cell in vitro DNA synthesis: evidence that DNA polymerase alpha is the only polymerase required for cellular DNA replication. Nucleic Acids Res. 1978 Jun;5(6):1933–1946. doi: 10.1093/nar/5.6.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wist E., Prydz H. The effect of aphidicolin on DNA synthesis in isolated HeLa cell nuclei. Nucleic Acids Res. 1979 Apr;6(4):1583–1590. doi: 10.1093/nar/6.4.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van der Vliet P. C., Kwant M. M. Role of DNA polymerase gamma in adenovirus DNA replication. Nature. 1978 Nov 30;276(5687):532–534. doi: 10.1038/276532a0. [DOI] [PubMed] [Google Scholar]

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