Abstract
Using an assay for recombination that measures deletion of a beta-galactosidase gene positioned between two directly repeated 350-bp sequences in plasmids transiently maintained in COS cells, we have found that replication from a simian virus 40 origin produces a high frequency of nonhomologous recombination. In contrast, plasmids replicating from a herpesvirus origin (oris) in COS cells superinfected with herpes simplex virus type 1 (HSV-1) show high levels of homologous recombination between the repeats and an enhanced recombinogenicity of the HSV-1 a sequence that is not seen during simian virus 40 replication. When the same assay was used to study recombination between 120- to 150-bp repeats in uninfected Vero cells, the level of recombination was extremely low or undetectable (< 0.03%), consistent with the fact that these repeats are smaller than the minimal efficient processing sequence for homologous recombination in mammalian cells. Recombination between these short repeats was easily measurable (0.5 to 0.8%) following HSV-1 infection, suggesting that there is an alteration of the recombination machinery. The frequency of recombination between repeats of the Uc-DR1 region, previously identified as the only segment of the HSV-1 a sequence indispensable for enhanced a-sequence recombination, was not significantly higher than that measured for other short sequences.
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- Ayares D., Spencer J., Schwartz F., Morse B., Kucherlapati R. Homologous recombination between autonomously replicating plasmids in mammalian cells. Genetics. 1985 Oct;111(2):375–388. doi: 10.1093/genetics/111.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown S. M., Ritchie D. A., Subak-Sharpe J. H. Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. J Gen Virol. 1973 Mar;18(3):329–346. doi: 10.1099/0022-1317-18-3-329. [DOI] [PubMed] [Google Scholar]
- Brown S. M., Subak-Sharpe J. H., Harland J., MacLean A. R. Analysis of intrastrain recombination in herpes simplex virus type 1 strain 17 and herpes simplex virus type 2 strain HG52 using restriction endonuclease sites as unselected markers and temperature-sensitive lesions as selected markers. J Gen Virol. 1992 Feb;73(Pt 2):293–301. doi: 10.1099/0022-1317-73-2-293. [DOI] [PubMed] [Google Scholar]
- Chen J., Young F., Bottaro A., Stewart V., Smith R. K., Alt F. W. Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus. EMBO J. 1993 Dec;12(12):4635–4645. doi: 10.1002/j.1460-2075.1993.tb06152.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng Y. L., Kalman L. V., Kaiser D. The dsg gene of Myxococcus xanthus encodes a protein similar to translation initiation factor IF3. J Bacteriol. 1994 Mar;176(5):1427–1433. doi: 10.1128/jb.176.5.1427-1433.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu G., Hayakawa H., Berg P. Electroporation for the efficient transfection of mammalian cells with DNA. Nucleic Acids Res. 1987 Feb 11;15(3):1311–1326. doi: 10.1093/nar/15.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davison A. J., Wilkie N. M. Nucleotide sequences of the joint between the L and S segments of herpes simplex virus types 1 and 2. J Gen Virol. 1981 Aug;55(Pt 2):315–331. doi: 10.1099/0022-1317-55-2-315. [DOI] [PubMed] [Google Scholar]
- Deiss L. P., Chou J., Frenkel N. Functional domains within the a sequence involved in the cleavage-packaging of herpes simplex virus DNA. J Virol. 1986 Sep;59(3):605–618. doi: 10.1128/jvi.59.3.605-618.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deiss L. P., Frenkel N. Herpes simplex virus amplicon: cleavage of concatemeric DNA is linked to packaging and involves amplification of the terminally reiterated a sequence. J Virol. 1986 Mar;57(3):933–941. doi: 10.1128/jvi.57.3.933-941.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delius H., Clements J. B. A partial denaturation map of herpes simplex virus type 1 DNA: evidence for inversions of the unique DNA regions. J Gen Virol. 1976 Oct;33(1):125–133. doi: 10.1099/0022-1317-33-1-125. [DOI] [PubMed] [Google Scholar]
- Dutch R. E., Bruckner R. C., Mocarski E. S., Lehman I. R. Herpes simplex virus type 1 recombination: role of DNA replication and viral a sequences. J Virol. 1992 Jan;66(1):277–285. doi: 10.1128/jvi.66.1.277-285.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dutch R. E., Zemelman B. V., Lehman I. R. Herpes simplex virus type 1 recombination: the Uc-DR1 region is required for high-level a-sequence-mediated recombination. J Virol. 1994 Jun;68(6):3733–3741. doi: 10.1128/jvi.68.6.3733-3741.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fromm M., Berg P. Deletion mapping of DNA regions required for SV40 early region promoter function in vivo. J Mol Appl Genet. 1982;1(5):457–481. [PubMed] [Google Scholar]
- Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
- Hayward G. S., Jacob R. J., Wadsworth S. C., Roizman B. Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4243–4247. doi: 10.1073/pnas.72.11.4243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honess R. W., Buchan A., Halliburton I. W., Watson D. H. Recombination and linkage between structural and regulatory genes of herpes simplex virus type 1: study of the functional organization of the genome. J Virol. 1980 Jun;34(3):716–742. doi: 10.1128/jvi.34.3.716-742.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huber H. E., Iida S., Arber W., Bickle T. A. Site-specific DNA inversion is enhanced by a DNA sequence element in cis. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3776–3780. doi: 10.1073/pnas.82.11.3776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacob R. J., Morse L. S., Roizman B. Anatomy of herpes simplex virus DNA. XII. Accumulation of head-to-tail concatemers in nuclei of infected cells and their role in the generation of the four isomeric arrangements of viral DNA. J Virol. 1979 Feb;29(2):448–457. doi: 10.1128/jvi.29.2.448-457.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenkins F. J., Roizman B. Herpes simplex virus 1 recombinants with noninverting genomes frozen in different isomeric arrangements are capable of independent replication. J Virol. 1986 Aug;59(2):494–499. doi: 10.1128/jvi.59.2.494-499.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. C., Simon M. I. Hin-mediated site-specific recombination requires two 26 bp recombination sites and a 60 bp recombinational enhancer. Cell. 1985 Jul;41(3):781–791. doi: 10.1016/s0092-8674(85)80059-3. [DOI] [PubMed] [Google Scholar]
- Kahmann R., Rudt F., Koch C., Mertens G. G inversion in bacteriophage Mu DNA is stimulated by a site within the invertase gene and a host factor. Cell. 1985 Jul;41(3):771–780. doi: 10.1016/s0092-8674(85)80058-1. [DOI] [PubMed] [Google Scholar]
- Kawasaki I., Bae Y. S., Eki T., Kim Y., Ikeda H. Homologous recombination of monkey alpha-satellite repeats in an in vitro simian virus 40 replication system: possible association of recombination with DNA replication. Mol Cell Biol. 1994 Jun;14(6):4173–4182. doi: 10.1128/mcb.14.6.4173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knipe D. M., Ruyechan W. T., Roizman B., Halliburton I. W. Molecular genetics of herpes simplex virus: demonstration of regions of obligatory and nonobligatory identity within diploid regions of the genome by sequence replacement and insertion. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3896–3900. doi: 10.1073/pnas.75.8.3896. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knipe D. M., Ruyechan W. T., Roizman B. Molecular genetics of herpes simplex virus. III. Fine mapping of a genetic locus determining resistance to phosphonoacetate by two methods of marker transfer. J Virol. 1979 Feb;29(2):698–704. doi: 10.1128/jvi.29.2.698-704.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin F. L., Sperle K., Sternberg N. Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process. Mol Cell Biol. 1984 Jun;4(6):1020–1034. doi: 10.1128/mcb.4.6.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liskay R. M., Letsou A., Stachelek J. L. Homology requirement for efficient gene conversion between duplicated chromosomal sequences in mammalian cells. Genetics. 1987 Jan;115(1):161–167. doi: 10.1093/genetics/115.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Longnecker R., Roizman B. Generation of an inverting herpes simplex virus 1 mutant lacking the L-S junction a sequences, an origin of DNA synthesis, and several genes including those specifying glycoprotein E and the alpha 47 gene. J Virol. 1986 May;58(2):583–591. doi: 10.1128/jvi.58.2.583-591.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mocarski E. S., Deiss L. P., Frenkel N. Nucleotide sequence and structural features of a novel US-a junction present in a defective herpes simplex virus genome. J Virol. 1985 Jul;55(1):140–146. doi: 10.1128/jvi.55.1.140-146.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mocarski E. S., Post L. E., Roizman B. Molecular engineering of the herpes simplex virus genome: insertion of a second L-S junction into the genome causes additional genome inversions. Cell. 1980 Nov;22(1 Pt 1):243–255. doi: 10.1016/0092-8674(80)90172-5. [DOI] [PubMed] [Google Scholar]
- Mocarski E. S., Roizman B. Herpesvirus-dependent amplification and inversion of cell-associated viral thymidine kinase gene flanked by viral a sequences and linked to an origin of viral DNA replication. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5626–5630. doi: 10.1073/pnas.79.18.5626. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mocarski E. S., Roizman B. Site-specific inversion sequence of the herpes simplex virus genome: domain and structural features. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7047–7051. doi: 10.1073/pnas.78.11.7047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parris D. S., Dixon R. A., Schaffer P. A. Physical mapping of herpes simplex virus type 1 ts mutants by marker rescue: correlation of the physical and genetic maps. Virology. 1980 Jan 30;100(2):275–287. doi: 10.1016/0042-6822(80)90519-x. [DOI] [PubMed] [Google Scholar]
- Poffenberger K. L., Tabares E., Roizman B. Characterization of a viable, noninverting herpes simplex virus 1 genome derived by insertion and deletion of sequences at the junction of components L and S. Proc Natl Acad Sci U S A. 1983 May;80(9):2690–2694. doi: 10.1073/pnas.80.9.2690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pogue-Geile K. L., Lee G. T., Spear P. G. Novel rearrangements of herpes simplex virus DNA sequences resulting from duplication of a sequence within the unique region of the L component. J Virol. 1985 Feb;53(2):456–461. doi: 10.1128/jvi.53.2.456-461.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [DOI] [PubMed] [Google Scholar]
- Rubnitz J., Subramani S. The minimum amount of homology required for homologous recombination in mammalian cells. Mol Cell Biol. 1984 Nov;4(11):2253–2258. doi: 10.1128/mcb.4.11.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarisky R. T., Weber P. C. Requirement for double-strand breaks but not for specific DNA sequences in herpes simplex virus type 1 genome isomerization events. J Virol. 1994 Jan;68(1):34–47. doi: 10.1128/jvi.68.1.34-47.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaffer P. A., Tevethia M. J., Benyesh-Melnick M. Recombination between temperature-sensitive mutants of herpes simplex virus type 1. Virology. 1974 Mar;58(1):219–228. doi: 10.1016/0042-6822(74)90156-1. [DOI] [PubMed] [Google Scholar]
- Serwe M., Sablitzky F. V(D)J recombination in B cells is impaired but not blocked by targeted deletion of the immunoglobulin heavy chain intron enhancer. EMBO J. 1993 Jun;12(6):2321–2327. doi: 10.1002/j.1460-2075.1993.tb05886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheldrick P., Berthelot N. Inverted repetitions in the chromosome of herpes simplex virus. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):667–678. doi: 10.1101/sqb.1974.039.01.080. [DOI] [PubMed] [Google Scholar]
- Shen P., Huang H. V. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics. 1986 Mar;112(3):441–457. doi: 10.1093/genetics/112.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sinden R. R., Pettijohn D. E., Francke B. Organization of herpes simplex virus type 1 deoxyribonucleic acid during replication probed in living cells with 4,5',8-trimethylpsoralen. Biochemistry. 1982 Aug 31;21(18):4484–4490. doi: 10.1021/bi00261a045. [DOI] [PubMed] [Google Scholar]
- Smiley J. R., Fong B. S., Leung W. C. Construction of a double-jointed herpes simplex viral DNA molecule: inverted repeats are required for segment inversion, and direct repeats promote deletions. Virology. 1981 Aug;113(1):345–362. doi: 10.1016/0042-6822(81)90161-6. [DOI] [PubMed] [Google Scholar]
- Stillman B. Initiation of eukaryotic DNA replication in vitro. Annu Rev Cell Biol. 1989;5:197–245. doi: 10.1146/annurev.cb.05.110189.001213. [DOI] [PubMed] [Google Scholar]
- Stow N. D., Subak-Sharpe J. H., Wilkie N. M. Physical mapping of herpes simplex virus type 1 mutations by marker rescue. J Virol. 1978 Oct;28(1):182–192. doi: 10.1128/jvi.28.1.182-192.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Subramani S. Analysis of recombination in mammalian cells using SV40 and SV40-derived vectors. Mutat Res. 1989 Mar-May;220(2-3):221–234. doi: 10.1016/0165-1110(89)90026-2. [DOI] [PubMed] [Google Scholar]
- Subramani S., Berg P. Homologous and nonhomologous recombination in monkey cells. Mol Cell Biol. 1983 Jun;3(6):1040–1052. doi: 10.1128/mcb.3.6.1040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Umene K. Recombination of the internal direct repeat element DR2 responsible for the fluidity of the a sequence of herpes simplex virus type 1. J Virol. 1991 Oct;65(10):5410–5416. doi: 10.1128/jvi.65.10.5410-5416.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Varmuza S. L., Smiley J. R. Signals for site-specific cleavage of HSV DNA: maturation involves two separate cleavage events at sites distal to the recognition sequences. Cell. 1985 Jul;41(3):793–802. doi: 10.1016/s0092-8674(85)80060-x. [DOI] [PubMed] [Google Scholar]
- WILDY P. Recombination with herpes simplex virus. J Gen Microbiol. 1955 Oct;13(2):346–360. doi: 10.1099/00221287-13-2-346. [DOI] [PubMed] [Google Scholar]
- Weber P. C., Challberg M. D., Nelson N. J., Levine M., Glorioso J. C. Inversion events in the HSV-1 genome are directly mediated by the viral DNA replication machinery and lack sequence specificity. Cell. 1988 Jul 29;54(3):369–381. doi: 10.1016/0092-8674(88)90200-0. [DOI] [PubMed] [Google Scholar]
- Weber P. C., Levine M., Glorioso J. C. Recombinogenic properties of herpes simplex virus type 1 DNA sequences resident in simian virus 40 minichromosomes. J Virol. 1990 Jan;64(1):300–306. doi: 10.1128/jvi.64.1.300-306.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wohlrab F., Chatterjee S., Wells R. D. The herpes simplex virus 1 segment inversion site is specifically cleaved by a virus-induced nuclear endonuclease. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6432–6436. doi: 10.1073/pnas.88.15.6432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wohlrab F., McLean M. J., Wells R. D. The segment inversion site of herpes simplex virus type 1 adopts a novel DNA structure. J Biol Chem. 1987 May 5;262(13):6407–6416. [PubMed] [Google Scholar]
- Wohlrab F., Wells R. D. Slight changes in conditions influence the family of non-B-DNA conformations of the herpes simplex virus type 1 DR2 repeats. J Biol Chem. 1989 May 15;264(14):8207–8213. [PubMed] [Google Scholar]