The DNA Polymerases Associated with the Adenovirus Type 2 Replication Complex: Effect of 2'-3'-dideoxythymidine-5'-triphosphate on Viral DNA Synthesis

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1979 Mar 1

PMID 440966

Citations 12

Authors

M M Abboud

M S Horwitz

Affiliations

Soon will be listed here.

Abstract

An adenovirus (Ad) DNA replication complex extracted from infected HeLa nuclei could be purified free of the bulk of intracellular DNA polymerase activity by sedimetation in neutral sucrose gradients. However, the replication complex still retained some alpha and gamma DNA-polymerase activity. Since this complex is inhibited by 2', 3' dideoxythymidine-5'-triphosphate (ddTTP), an inhibitor of DNA polymerase gamma, a functional role for this enzyme in Ad DNA replication is suggested. Similar inhibition by ddTTP in intact Ad infected nuclei and comparable inhibition of Ad DNA synthesis in whole cells by dideoxythymidine (ddThy) are consistent with a role for DNA polymerase gamma. Uninfected HeLa nuclei or whole cells are not similarly inhibited by ddTTP or DDThy respectively. Such data does not rule out an additional functional role for other DNA polymerases, and recent experiments from this laboratory (1) suggest that DNA polymerase alpha is also involved in Ad DNA synthesis.

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References

van der Vliet P, Kwant M . Role of DNA polymerase gamma in adenovirus DNA replication. Nature. 1978; 276(5687):532-4. DOI: 10.1038/276532a0. View

Waqar M, Evans M, Huberman J . 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; 5(6):1933-46. PMC: 342135. DOI: 10.1093/nar/5.6.1933. View

Edenberg H, Anderson S, DePamphilis M . Involvement of DNA polymerase alpha in simian virus 40 DNA replication. J Biol Chem. 1978; 253(9):3273-80. View

Abboud M, Sim W, Loeb L, Mildvan A . Apparent suicidal inactivation of DNA polymerase by adenosine 2',3'-riboepoxide 5'-triphosphate. J Biol Chem. 1978; 253(10):3415-21. View

Frenkel G . Adenovirus DNA synthesis in vitro in an isolated complex. J Virol. 1978; 25(1):459-63. PMC: 353950. DOI: 10.1128/JVI.25.1.459-463.1978. View

Weissbach A . Eukaryotic DNA polymerases. Annu Rev Biochem. 1977; 46:25-47. DOI: 10.1146/annurev.bi.46.070177.000325. View

Brison O, Kedinger C, Wilhelm J . Enzymatic properties of viral replication complexes isolated from adenovirus type 2-infected HeLa cell nuclei. J Virol. 1977; 24(2):423-35. PMC: 515951. DOI: 10.1128/JVI.24.2.423-435.1977. View

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; 252(22):7947-54. View

Yamashita T, Arens M, Green M . Adenovirus deoxyribonucleic acid replication. Isolation of a soluble replication system and analysis of the in vitro DNA product. J Biol Chem. 1977; 252(22):7940-6. View

10.

Dube D, Seal G, Loeb L . Differential heat sensitivity of mammalian DNA polymerases. Biochem Biophys Res Commun. 1976; 76(2):483-7. DOI: 10.1016/0006-291x(77)90750-1. View

11.

Bolden A, Noy G, Weissbach A . DNA polymerase of mitochondria is a gamma-polymerase. J Biol Chem. 1977; 252(10):3351-6. View

12.

Horwitz M . Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro. Proc Natl Acad Sci U S A. 1978; 75(9):4291-5. PMC: 336099. DOI: 10.1073/pnas.75.9.4291. View

13.

Kaplan L, Kelinman R, Horwitz M . Replication of adenovirus type 2 DNA in vitro. Proc Natl Acad Sci U S A. 1977; 74(10):4425-9. PMC: 431955. DOI: 10.1073/pnas.74.10.4425. View

14.

Lechner R, Kelly Jr T . The structure of replicating adenovirus 2 DNA molecules. Cell. 1977; 12(4):1007-20. DOI: 10.1016/0092-8674(77)90165-9. View

15.

Byars N, Kidson C . DNA chain termination by 2',3'-dideoxythymidine in replicating mammalian cells. Biochemistry. 1975; 14(14):3159-64. DOI: 10.1021/bi00685a019. View

16.

Matsukage A, Bohn E, Wilson S . On the DNA polymerase III of mouse myeloma: partial purification and characterization. Biochemistry. 1975; 14(5):1006-20. DOI: 10.1021/bi00676a020. View

17.

Spadari S, Weissbach A . The interrelation between DNA synthesis and various DNA polymerase activities in synchronized HeLa cells. J Mol Biol. 1974; 86(1):11-20. DOI: 10.1016/s0022-2836(74)80003-3. View

18.

TREMBLAY G, Daniels M, Schaechter M . Isolation of a cell membrane-DNA-nascent RNA complex from bacteria. J Mol Biol. 1969; 40(1):65-76. DOI: 10.1016/0022-2836(69)90296-4. View

19.

Ito K, Arens M, Green M . Isolation of DNA polymerase gamma from an adenovirus 2 DNA replication complex. J Virol. 1975; 15(6):1507-10. PMC: 354619. DOI: 10.1128/JVI.15.6.1507-1510.1975. View

20.

Matsukage A, Bohn E, Wilson S . Differential sensitivity of low molecular weight DNA polymerase to sulfhydryl-blocking reagents. Biochim Biophys Acta. 1975; 383(3):338-43. DOI: 10.1016/0005-2787(75)90062-3. View