Home LiteratureArticle Details
PMID: 2033669 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Origin of adeno-associated virus DNA replication is a target of carcinogen-inducible DNA amplification.

Journal of virology ·Vol. 65 ·No. 6 ·1991-06-00 ·Pages 3175-84

Yalkinoglu AO, Zentgraf H, Hübscher U

Abstract

DNA amplification of the helper-dependent parvovirus AAV (adeno-associated virus) can be induced by a variety of genotoxic agents in the absence of coinfecting helper virus. Here we investigated whether the origin of AAV type 2 DNA replication cloned into a plasmid is sufficient to promote replication activity in cells treated by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). A pUC19-based plasmid, designated pA2Y1, which contains the left terminal repeat sequences (TRs) representing the AAV origin of replication and the p5 and p19 promoter but lacks any functional parvoviral genes is shown to confer replication activity and to allow selective DNA amplification in carcinogen-treated cells. Following transfection of plasmid pA2Y1 or plasmid pUC19 as a control, density labeling by a bromodeoxyuridine and DpnI resistance assay suggested a semi-conservative mode of replication of the AAV origin-containing plasmid. Furthermore, the amount of DpnI-resistant full-length pA2Y1 DNA molecules was increased by MNNG treatment of cells in a dose-dependent manner. In addition, DNA synthesis of plasmid pA2Y1 was studied in vitro. Extracts derived from MNNG-treated CHO-9 and L1210 cells displayed greater synthesis of DpnI-resistant full-length pA2Y1 molecules than did nontreated controls. Experiments with specific enzyme inhibitors suggested that the reaction is largely dependent on DNA polymerase alpha, DNA primase, and DNA topoisomerase I. Furthermore, restriction endonuclease mapping analysis of the in vitro reaction products revealed the occurrence of specific initiation at the AAV origin of DNA replication. Though elongation was not very extensive, extracts from carcinogen-treated cells markedly amplified the AAV origin region. Our results, including electron microscopic examination, suggest that the AAV origin/terminal repeat structure is recognized by the cellular DNA replicative machinery induced or modulated by carcinogen treatment in the absence of parvoviral gene products.

MeSH Terms
Adenoviridae/drug effects,genetics,growth & development Animals Cells, Cultured Cricetinae DNA Replication/drug effects DNA, Viral/biosynthesis,drug effects Deoxyribonucleases, Type II Site-Specific Gene Amplification/drug effects Methylnitronitrosoguanidine/pharmacology Nucleic Acid Conformation Plasmids Promoter Regions, Genetic Repetitive Sequences, Nucleic Acid Transfection Virus Replication
Chemicals
DNA, Viral Methylnitronitrosoguanidine endodeoxyribonuclease DpnI Deoxyribonucleases, Type II Site-Specific
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yalkinoglu A O
Institut für Virusforschung/Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Zentgraf H
Hübscher U
References (64)
64 references, click to expand
  1. Selective extraction of polyoma DNA from infected mouse cell cultures.
    J Mol Biol. 1967 Jun 14;26(2):365-9 PMID: 4291934
  2. Replication of adeno-associated virus in synchronized cells without the addition of a helper virus.
    J Virol. 1987 Apr;61(4):972-81 PMID: 3029431
  3. Concatemers of alternating plus and minus strands are intermediates in adenovirus-associated virus DNA synthesis.
    Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 PMID: 1062784
  4. Origin and termination of adeno-associated virus DNA replication.
    Virology. 1977 May 15;78(2):488-99 PMID: 867815
  5. HeLa cell DNA polymerases: the effect of cycloheximide in vivo and detection of a new form of DNA polymerase alpha.
    Biochim Biophys Acta. 1977 Jul 5;477(1):70-83 PMID: 884108
  6. Involvement of DNA polymerase alpha in simian virus 40 DNA replication.
    J Biol Chem. 1978 May 10;253(9):3273-80 PMID: 205546
  7. The delta subunit of Escherichia coli DNA polymerase III holoenzyme is the dnaX gene product.
    Proc Natl Acad Sci U S A. 1979 Dec;76(12):6284-8 PMID: 160563
  8. Nucleotide sequence of the inverted terminal repetition in adeno-associated virus DNA.
    J Virol. 1980 May;34(2):402-9 PMID: 6246271
  9. DNA amplification in drug resistant cells and in tumours.
    Cancer Surv. 1986;5(1):1-23 PMID: 3297310
  10. Adeno-associated virus gene expression inhibits cellular transformation by heterologous genes.
    Mol Cell Biol. 1987 Apr;7(4):1320-5 PMID: 3037312
  11. A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication.
    J Virol. 1987 Oct;61(10):3096-101 PMID: 3041032
  12. Autonomous replication of plasmids bearing monkey DNA origin-enriched sequences.
    Proc Natl Acad Sci U S A. 1987 Oct;84(19):6668-72 PMID: 3477798
  13. The adeno-associated virus rep gene inhibits replication of an adeno-associated virus/simian virus 40 hybrid genome in cos-7 cells.
    J Virol. 1988 May;62(5):1705-12 PMID: 2833621
  14. DNA amplification of adeno-associated virus as a response to cellular genotoxic stress.
    Cancer Res. 1988 Jun 1;48(11):3123-9 PMID: 2835153
  15. Adeno-associated virus general transduction vectors: analysis of proviral structures.
    J Virol. 1988 Jun;62(6):1963-73 PMID: 2835501
  16. In vitro excision of adeno-associated virus DNA from recombinant plasmids: isolation of an enzyme fraction from HeLa cells that cleaves DNA at poly(G) sequences.
    Mol Cell Biol. 1988 Jun;8(6):2513-22 PMID: 2841582
  17. Effect of anti-cruciform DNA monoclonal antibodies on DNA replication.
    EMBO J. 1988 Jun;7(6):1837-44 PMID: 3169006
  18. Regulation of adeno-associated virus DNA replication.
    Biochim Biophys Acta. 1988 Dec 20;951(2-3):425-9 PMID: 2850017
  19. Replication of adeno-associated virus in cells irradiated with UV light at 254 nm.
    J Virol. 1989 Mar;63(3):1023-30 PMID: 2536816
  20. Identification of nuclear proteins that specifically interact with adeno-associated virus type 2 inverted terminal repeat hairpin DNA.
    J Virol. 1989 Jul;63(7):3034-9 PMID: 2542611
  21. Factors that bind to adeno-associated virus terminal repeats.
    J Virol. 1989 Jul;63(7):3095-104 PMID: 2542617
  22. Purification of replication protein C, a cellular protein involved in the initial stages of simian virus 40 DNA replication in vitro.
    Proc Natl Acad Sci U S A. 1989 May;86(10):3584-8 PMID: 2542940
  23. Expression from the adeno-associated virus p5 and p19 promoters is negatively regulated in trans by the rep protein.
    J Virol. 1989 Oct;63(10):4450-4 PMID: 2550677
  24. Initiation of eukaryotic DNA replication in vitro.
    Annu Rev Cell Biol. 1989;5:197-245 PMID: 2557059
  25. Carcinogen-induced DNA amplification in vitro: overreplication of the simian virus 40 origin region in extracts from carcinogen-treated CO60 cells.
    Mol Cell Biol. 1990 Jan;10(1):75-83 PMID: 2152968
  26. UV-induced early-domain binding factor as the limiting component of simian virus 40 DNA amplification in rodent cells.
    Mol Cell Biol. 1989 Nov;9(11):4812-18 PMID: 2557541
  27. Requirement for two DNA polymerases in the replication of simian virus 40 DNA in vitro.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9742-6 PMID: 2574863
  28. In vitro resolution of covalently joined AAV chromosome ends.
    Cell. 1990 Jan 12;60(1):105-13 PMID: 2153052
  29. Adeno-associated parvoviruses inhibit growth of cells derived from malignant human tumors.
    Int J Cancer. 1990 Jan 15;45(1):190-4 PMID: 2153636
  30. The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity.
    Cell. 1990 May 4;61(3):447-57 PMID: 2159383
  31. The adeno-associated virus rep gene suppresses herpes simplex virus-induced DNA amplification.
    J Virol. 1990 Jun;64(6):3012-8 PMID: 2159559
  32. Inhibition of N-methyl-N'-nitro-N-nitrosoguanidine-induced methotrexate and adriamycin resistance in CHO cells by adeno-associated virus type 2.
    Int J Cancer. 1990 Jun 15;45(6):1195-203 PMID: 2161803
  33. Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin.
    Nature. 1990 Aug 9;346(6284):534-9 PMID: 2165567
  34. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression.
    J Virol. 1989 Sep;63(9):3822-8 PMID: 2547998
  35. The adeno-associated virus Rep78 gene inhibits cellular transformation induced by bovine papillomavirus.
    Virology. 1989 Sep;172(1):253-61 PMID: 2549714
  36. Amplification of bovine papillomavirus DNA by N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus.
    Virology. 1989 Sep;172(1):73-81 PMID: 2549724
  37. Animal virus DNA replication.
    Annu Rev Biochem. 1989;58:671-717 PMID: 2549858
  38. Integration of the adeno-associated virus genome into cellular DNA in latently infected human Detroit 6 cells.
    J Virol. 1980 Feb;33(2):739-48 PMID: 6251245
  39. The inverted repeat as a recognizable structural feature in supercoiled DNA molecules.
    Proc Natl Acad Sci U S A. 1980 Nov;77(11):6468-72 PMID: 6256738
  40. Cruciform structures in supercoiled DNA.
    Nature. 1981 Feb 5;289(5797):466-70 PMID: 7464915
  41. Inhibition of adenovirus oncogenicity in hamsters by adeno-associated virus DNA.
    J Natl Cancer Inst. 1981 Dec;67(6):1323-6 PMID: 6273635
  42. Carcinogen-mediated amplification of viral DNA sequences in simian virus 40-transformed Chinese hamster embryo cells.
    Proc Natl Acad Sci U S A. 1981 Oct;78(10):6144-8 PMID: 6273853
  43. Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase alpha.
    J Biol Chem. 1982 Jul 25;257(14):8386-90 PMID: 7085672
  44. Benzo[a]pyrene induction of extrachromosomal viral DNA synthesis in rat cells transformed by polyoma virus.
    Carcinogenesis. 1983;4(5):587-93 PMID: 6303617
  45. Cloning of infectious adeno-associated virus genomes in bacterial plasmids.
    Gene. 1983 Jul;23(1):65-73 PMID: 6352411
  46. Gene amplification, drug resistance, and cancer.
    Cancer Res. 1984 May;44(5):1735-42 PMID: 6713376
  47. UV Irradiation induces an activity which stimulates Simian virus 40 rescue upon cell fusion.
    Mol Cell Biol. 1984 Jun;4(6):1159-62 PMID: 6330532
  48. Simian virus 40 DNA replication in vitro.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):6973-7 PMID: 6095264
  49. SOS response in mammalian cells.
    Cancer Invest. 1985;3(2):163-74 PMID: 2986797
  50. Selective DNA-amplification induced by carcinogens (initiators): evidence for a role of proteases and DNA polymerase alpha.
    Int J Cancer. 1985 Jul 15;36(1):85-91 PMID: 3894246
  51. Enhanced induction of SV40 replication from transformed mammalian cells by fusion with UV-irradiated untransformed cells.
    Mutat Res. 1985 Aug;151(1):1-8 PMID: 2991760
  52. Simian virus 40 DNA replication in vitro: specificity of initiation and evidence for bidirectional replication.
    Mol Cell Biol. 1985 Jun;5(6):1238-46 PMID: 2993858
  53. Elucidation of the mechanism of selective inhibition of mammalian DNA polymerase alpha by 2-butylanilinopurines: development and characterization of 2-(p-n-butylanilino)adenine and its deoxyribonucleotides.
    Nucleic Acids Res. 1985 Sep 11;13(17):6331-42 PMID: 3931053
  54. Large inverted duplications are associated with gene amplification.
    Cell. 1986 May 9;45(3):425-30 PMID: 2870814
  55. Carcinogen induced asynchronous replication of polyoma DNA is mediated by a trans-acting factor.
    Carcinogenesis. 1986 Jun;7(6):1011-7 PMID: 3011304
  56. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus.
    Virology. 1986 Jul 15;152(1):110-7 PMID: 3012864
  57. Positive and negative autoregulation of the adeno-associated virus type 2 genome.
    J Virol. 1986 Oct;60(1):251-8 PMID: 3018288
  58. DNA helicase activity of SV40 large tumor antigen.
    EMBO J. 1986 Aug;5(8):1939-44 PMID: 3019672
  59. Latent infection of KB cells with adeno-associated virus type 2.
    J Virol. 1986 Nov;60(2):515-24 PMID: 3021985
  60. Oncogene amplification in tumor cells.
    Adv Cancer Res. 1986;47:235-81 PMID: 3022564
  61. Negative and positive regulation in trans of gene expression from adeno-associated virus vectors in mammalian cells by a viral rep gene product.
    Mol Cell Biol. 1986 Aug;6(8):2884-94 PMID: 3491293
  62. Alpha-radiation-induced amplification of integrated SV40 sequences is mediated by a trans-acting mechanism.
    Int J Cancer. 1987 Jan 15;39(1):94-8 PMID: 3025112
  63. Parvovirus gene regulation.
    J Gen Virol. 1987 Mar;68 ( Pt 3):601-14 PMID: 3546593
  64. Simplified quantitative electron microscopy of biopolymers.
    Biopolymers. 1970;9(3):373-9 PMID: 5417647
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.65.6.3175-3184.1991
Published
1991-06-00
Pages
3175-84
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240974
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.65.6.3175-3184.1991 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2