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. 1986 Nov 11;14(21):8361–8371. doi: 10.1093/nar/14.21.8361

DNA amplification--deletion in a spontaneous mutation of the hamster aprt locus: structure and sequence of the novel joint.

J Nalbantoglu, M Meuth
PMCID: PMC311864  PMID: 3024103

Abstract

In a collection of spontaneous mutants of Chinese hamster ovary cells selected for deficiency in adenine phosphoribosyl transferase (aprt) activity, one was detected having not only a deletion of aprt coding sequences but also an apparent amplification of remaining sequences. The HindIII fragment bearing the novel joint was cloned and sequenced revealing a complex gene rearrangement. A deletion of at least 9 kb extending upstream from the aprt locus is accompanied by an inverted duplication of flanking sequences 672 bp downstream from the novel joint. This unit is amplified three to four times with the net result of some sequences being increased as much as eight fold in copy number because of the duplication. The fidelity of the sequences involved is preserved. We propose a model which could account for this inverted duplication.

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Selected References

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

  1. Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707–1711. doi: 10.1073/pnas.80.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradley W. E., Letovanec D. High-frequency nonrandom mutational event at the adenine phosphoribosyltransferase (aprt) locus of sib-selected CHO variants heterozygous for aprt. Somatic Cell Genet. 1982 Jan;8(1):51–66. doi: 10.1007/BF01538650. [DOI] [PubMed] [Google Scholar]
  4. Brenner D. A., Smigocki A. C., Camerini-Otero R. D. Double-strand gap repair results in homologous recombination in mouse L cells. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1762–1766. doi: 10.1073/pnas.83.6.1762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown D. D., Dawid I. B. Specific gene amplification in oocytes. Oocyte nuclei contain extrachromosomal replicas of the genes for ribosomal RNA. Science. 1968 Apr 19;160(3825):272–280. doi: 10.1126/science.160.3825.272. [DOI] [PubMed] [Google Scholar]
  6. Brutlag D. L., Clayton J., Friedland P., Kedes L. H. SEQ: a nucleotide sequence analysis and recombination system. Nucleic Acids Res. 1982 Jan 11;10(1):279–294. doi: 10.1093/nar/10.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dush M. K., Sikela J. M., Khan S. A., Tischfield J. A., Stambrook P. J. Nucleotide sequence and organization of the mouse adenine phosphoribosyltransferase gene: presence of a coding region common to animal and bacterial phosphoribosyltransferases that has a variable intron/exon arrangement. Proc Natl Acad Sci U S A. 1985 May;82(9):2731–2735. doi: 10.1073/pnas.82.9.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ford M., Davies B., Griffiths M., Wilson J., Fried M. Isolation of a gene enhancer within an amplified inverted duplication after "expression selection". Proc Natl Acad Sci U S A. 1985 May;82(10):3370–3374. doi: 10.1073/pnas.82.10.3370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ford M., Fried M. Large inverted duplications are associated with gene amplification. Cell. 1986 May 9;45(3):425–430. doi: 10.1016/0092-8674(86)90328-4. [DOI] [PubMed] [Google Scholar]
  10. Nalbantoglu J., Goncalves O., Meuth M. Structure of mutant alleles at the aprt locus of Chinese hamster ovary cells. J Mol Biol. 1983 Jul 5;167(3):575–594. doi: 10.1016/s0022-2836(83)80099-0. [DOI] [PubMed] [Google Scholar]
  11. Nalbantoglu J., Hartley D., Phear G., Tear G., Meuth M. Spontaneous deletion formation at the aprt locus of hamster cells: the presence of short sequence homologies and dyad symmetries at deletion termini. EMBO J. 1986 Jun;5(6):1199–1204. doi: 10.1002/j.1460-2075.1986.tb04347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nalbantoglu J., Phear G. A., Meuth M. Nucleotide sequence of hamster adenine phosphoribosyl transferase (aprt) gene. Nucleic Acids Res. 1986 Feb 25;14(4):1914–1914. doi: 10.1093/nar/14.4.1914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  14. Pelicci P. G., Lanfrancone L., Brathwaite M. D., Wolman S. R., Dalla-Favera R. Amplification of the c-myb oncogene in a case of human acute myelogenous leukemia. Science. 1984 Jun 8;224(4653):1117–1121. doi: 10.1126/science.6585957. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Schimke R. T. Gene amplification in cultured animal cells. Cell. 1984 Jul;37(3):705–713. doi: 10.1016/0092-8674(84)90406-9. [DOI] [PubMed] [Google Scholar]
  17. Shiloh Y., Shipley J., Brodeur G. M., Bruns G., Korf B., Donlon T., Schreck R. R., Seeger R., Sakai K., Latt S. A. Differential amplification, assembly, and relocation of multiple DNA sequences in human neuroblastomas and neuroblastoma cell lines. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3761–3765. doi: 10.1073/pnas.82.11.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Spradling A. C., Mahowald A. P. Amplification of genes for chorion proteins during oogenesis in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1096–1100. doi: 10.1073/pnas.77.2.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stark G. R., Wahl G. M. Gene amplification. Annu Rev Biochem. 1984;53:447–491. doi: 10.1146/annurev.bi.53.070184.002311. [DOI] [PubMed] [Google Scholar]
  20. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zieg J., Clayton C. E., Ardeshir F., Giulotto E., Swyryd E. A., Stark G. R. Properties of single-step mutants of Syrian hamster cell lines resistant to N-(phosphonacetyl)-L-aspartate. Mol Cell Biol. 1983 Nov;3(11):2089–2098. doi: 10.1128/mcb.3.11.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]

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