Abstract
We analyzed two functionally defective mouse kappa light chain gene variants previously shown to contain novel insertions of repetitive DNA in their intervening sequences [Hawley, R. G., Shulman, M. J., Murialdo, H., Gibson, D. M. & Hozumi, N. (1982) Proc. Natl. Acad. Sci. USA 79, 7425-7429]. Heteroduplex analysis of the cloned genes shows that the insertions consist of intracisternal A-particle (IAP) genetic elements. Each insertion includes an IAP 5' long terminal repeat (LTR) sequence and extends to a characteristic IAP internal BamHI site where the IAP sequence is interrupted because the mutant genes were cloned from complete BamHI digests of the cellular DNAs. Restriction enzyme mapping indicates that the 5' LTR boundaries of the inserted IAP elements correspond closely to the previously determined rearrangement sites in the mutant genes. The IAP insertions in the two mutants can be distinguished by restriction-site differences and by the fact that one of them contains a deletion that is absent in the other. Nucleotide sequence data are presented for the LTRs of one full-length IAP gene copy randomly selected from a mouse genomic DNA library. These LTRs show many features typical of known integrated retroviral terminal repeat units, and the entire gene is bracketed by short direct repeats within the adjacent cellular DNA. Thus, the findings show that IAP genetic elements can appear in new locations in mouse cellular DNA and suggest that this may occur through a process of proviral insertion.
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Selected References
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- Alwine J. C., Kemp D. J., Parker B. A., Reiser J., Renart J., Stark G. R., Wahl G. M. Detection of specific RNAs or specific fragments of DNA by fractionation in gels and transfer to diazobenzyloxymethyl paper. Methods Enzymol. 1979;68:220–242. doi: 10.1016/0076-6879(79)68017-5. [DOI] [PubMed] [Google Scholar]
- Benoist C., O'Hare K., Breathnach R., Chambon P. The ovalbumin gene-sequence of putative control regions. Nucleic Acids Res. 1980 Jan 11;8(1):127–142. doi: 10.1093/nar/8.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biczysko W., Pienkowski M., Solter D., Koprowski H. Virus particles in early mouse embryos. J Natl Cancer Inst. 1973 Sep;51(3):1041–1050. doi: 10.1093/jnci/51.3.1041. [DOI] [PubMed] [Google Scholar]
- Boseley P. G., Moss T., Birnstiel M. L. 5'-Labeling and poly(dA) tailing. Methods Enzymol. 1980;65(1):478–494. [PubMed] [Google Scholar]
- Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
- Calos M. P., Miller J. H. Transposable elements. Cell. 1980 Jul;20(3):579–595. doi: 10.1016/0092-8674(80)90305-0. [DOI] [PubMed] [Google Scholar]
- Chase D. G., Pikó L. Expression of A- and C-type particles in early mouse embryos. J Natl Cancer Inst. 1973 Dec;51(6):1971–1975. doi: 10.1093/jnci/51.6.1971. [DOI] [PubMed] [Google Scholar]
- Cole M. D., Ono M., Huang R. C. Intracisternal A-particle genes: structure of adjacent genes and mapping of the boundaries of the transcriptional unit. J Virol. 1982 Apr;42(1):123–130. doi: 10.1128/jvi.42.1.123-130.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cole M. D., Ono M., Huang R. C. Terminally redundant sequences in cellular intracisternal A-particle genes. J Virol. 1981 May;38(2):680–687. doi: 10.1128/jvi.38.2.680-687.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M., Hozumi N. Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. Dilute (d) coat colour mutation of DBA/2J mice is associated with the site of integration of an ecotropic MuLV genome. Nature. 1981 Oct 1;293(5831):370–374. doi: 10.1038/293370a0. [DOI] [PubMed] [Google Scholar]
- Kuff E. L., Leuders K. K., Ozer H. L., Wivel N. A. Some structural and antigenic properties of intracisternal A particles occurring in mouse tumors (complement fixation-immunodiffusion-neuroblastoma-plasma-cell tumor). Proc Natl Acad Sci U S A. 1972 Jan;69(1):218–222. doi: 10.1073/pnas.69.1.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuff E. L., Smith L. A., Lueders K. K. Intracisternal A-particle genes in Mus musculus: a conserved family of retrovirus-like elements. Mol Cell Biol. 1981 Mar;1(3):216–227. doi: 10.1128/mcb.1.3.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuff E. L., Wivel N. A., Lueders K. K. The extraction of intracisternal A-particles from a mouse plasma-cell tumor. Cancer Res. 1968 Oct;28(10):2137–2148. [PubMed] [Google Scholar]
- Lueders K. K., Kuff E. L. Intracisternal A-particle genes: identification in the genome of Mus musculus and comparison of multiple isolates from a mouse gene library. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3571–3575. doi: 10.1073/pnas.77.6.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lueders K. K., Kuff E. L. Sequences associated with intracisternal A particles are reiterated in the mouse genome. Cell. 1977 Dec;12(4):963–972. doi: 10.1016/0092-8674(77)90161-1. [DOI] [PubMed] [Google Scholar]
- Max E. E., Maizel J. V., Jr, Leder P. The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse kappa immunoglobulin J and C region genes. J Biol Chem. 1981 May 25;256(10):5116–5120. [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Minna J. D., Lueders K. K., Kuff E. L. Expression of genes for intracisternal A-particle antigen in somatic cell hybrids. J Natl Cancer Inst. 1974 Apr;52(4):1211–1217. doi: 10.1093/jnci/52.4.1211. [DOI] [PubMed] [Google Scholar]
- Neel B. G., Hayward W. S., Robinson H. L., Fang J., Astrin S. M. Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion. Cell. 1981 Feb;23(2):323–334. doi: 10.1016/0092-8674(81)90128-8. [DOI] [PubMed] [Google Scholar]
- Ono M., Cole M. D., White A. T., Huang R. C. Sequence organization of cloned intracisternal A particle genes. Cell. 1980 Sep;21(2):465–473. doi: 10.1016/0092-8674(80)90483-3. [DOI] [PubMed] [Google Scholar]
- Paterson B. M., Segal S., Lueders K. K., Kuff E. L. RNA associated with murine intracisternal type A particles codes for the main particle protein. J Virol. 1978 Jul;27(1):118–126. doi: 10.1128/jvi.27.1.118-126.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Proudfoot N. J., Brownlee G. G. Sequence at the 3' end of globin mRNA shows homology with immunoglobulin light chain mRNA. Nature. 1974 Nov 29;252(5482):359–362. doi: 10.1038/252359a0. [DOI] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Rimm D. L., Horness D., Kucera J., Blattner F. R. Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene. 1980 Dec;12(3-4):301–309. doi: 10.1016/0378-1119(80)90113-4. [DOI] [PubMed] [Google Scholar]
- Seed B. Diazotizable arylamine cellulose papers for the coupling and hybridization of nucleic acids. Nucleic Acids Res. 1982 Mar 11;10(5):1799–1810. doi: 10.1093/nar/10.5.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapiro J. A. Molecular model for the transposition and replication of bacteriophage Mu and other transposable elements. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1933–1937. doi: 10.1073/pnas.76.4.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shen-Ong G. L., Cole M. D. Differing populations of intracisternal A-particle genes in myeloma tumors and mouse subspecies. J Virol. 1982 May;42(2):411–421. doi: 10.1128/jvi.42.2.411-421.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swanstrom R., DeLorbe W. J., Bishop J. M., Varmus H. E. Nucleotide sequence of cloned unintegrated avian sarcoma virus DNA: viral DNA contains direct and inverted repeats similar to those in transposable elements. Proc Natl Acad Sci U S A. 1981 Jan;78(1):124–128. doi: 10.1073/pnas.78.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tu C. P., Cohen S. N. 3'-end labeling of DNA with [alpha-32P]cordycepin-5'-triphosphate. Gene. 1980 Jul;10(2):177–183. doi: 10.1016/0378-1119(80)90135-3. [DOI] [PubMed] [Google Scholar]
- Varmus H. E. Form and function of retroviral proviruses. Science. 1982 May 21;216(4548):812–820. doi: 10.1126/science.6177038. [DOI] [PubMed] [Google Scholar]
- Varmus H. E., Quintrell N., Ortiz S. Retroviruses as mutagens: insertion and excision of a nontransforming provirus alter expression of a resident transforming provirus. Cell. 1981 Jul;25(1):23–36. doi: 10.1016/0092-8674(81)90228-2. [DOI] [PubMed] [Google Scholar]
- Wilson S. H., Bohn E. W., Matsukage A., Lueders K. K., Kuff E. L. Studies on the relationship between deoxyribonucleic acid polymerase activity and intracisternal A-type particles in mouse myeloma. Biochemistry. 1974 Mar 12;13(6):1087–1094. doi: 10.1021/bi00703a005. [DOI] [PubMed] [Google Scholar]
- Wong-Staal F., Reitz M. S., Jr, Trainor C. D., Gallo R. C. Murine intracisternal type A particles: a biochemical characterization. J Virol. 1975 Oct;16(4):887–896. doi: 10.1128/jvi.16.4.887-896.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang S. S., Wivel N. A. Physicochemical analysis of the deoxyribonucleic acid product of murine intracisternal A particle RNA-directed DNA polymerase. Biochim Biophys Acta. 1976 Oct 4;447(2):167–174. doi: 10.1016/0005-2787(76)90340-3. [DOI] [PubMed] [Google Scholar]
- Yotsuyanagi Y., Szöllösi D. Early mouse embryo intracisternal particle: Fourth type of retrovirus-like particle associated with the mouse. J Natl Cancer Inst. 1981 Sep;67(3):677–685. [PubMed] [Google Scholar]
- de Wet J. R., Daniels D. L., Schroeder J. L., Williams B. G., Denniston-Thompson K., Moore D. D., Blattner F. R. Restriction maps for twenty-one Charon vector phages. J Virol. 1980 Jan;33(1):401–410. doi: 10.1128/jvi.33.1.401-410.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]