Effect of chromosomal position on amplification of transfected genes in animal cells

@article{Wahl1984EffectOC,
  title={Effect of chromosomal position on amplification of transfected genes in animal cells},
  author={Geoffrey M. Wahl and Bruno Vincent and Margaret L. DeRose},
  journal={Nature},
  year={1984},
  volume={307},
  pages={516-520}
}
A single protein (CAD) contains the first three enzymatic activities of de novo undine biosynthesis. The chromosomal location of CAD genes introduced into Chinese hamster ovary cells significantly affects the frequency and cytogenetic result of their amplification. The amplification frequency in one transformant is 100-fold that of the others; in another, amplification of donated genes inserted near a centromere results in chromosome instability and rearrangements. 
View on Springer
ncbi.nlm.nih.gov
120 Citations
Background Citations
25
Methods Citations
5

120 Citations

Effect of genomic position on amplification of the DFR1 gene in Saccharomyces cerevisiae.
TLDR
In spite of a relative wealth of information about the distribution and arrangement of amplicons observed in MTXR cells, the authors know very little about endogenous factors which affect the frequency of DHFR amplification-nor do they understand, at the molecular level, the process of resolution of early events into the final amplicon structures observed in drug-resistant cells.
Unstable and stable CAD gene amplification: importance of flanking sequences and nuclear environment in gene amplification
TLDR
It is reported for the first time that the CAD gene is amplified unstably in mouse cells, that the degree of instability varies greatly between clones, and that minute chromosomes and highly unstable chromosomelike structures contain the amplified sequences.
Plasmid amplification-promoting sequences from the origin region of Chinese hamster dihydrofolate reductase gene do not promote position-independent chromosomal gene amplification
TLDR
It is suggested that the mechanism that mediates the experiment of episomal plasmid DNA amplification does not contribute to the early steps of chromosomal gene amplification.
Site-specific integration of H-ras in transformed rat embryo cells.
TLDR
All seven lines showed a common integration site for ras on the q arm of rat chromosome 3 (3q12), though some lines also had other sites of integration and in four of the lines integration of ras was accompanied by deletion of the p arm of chromosome 3 or its possible translocation to chromosome 12.
Localization of a cis-acting element responsible for the developmentally regulated amplification of drosophila chorion genes
Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosome 3: evidence for the role of chromosome rearrangement in gene amplification
TLDR
Observations suggested that both functionally related, isometallothionein loci are linked on Chinese hamster chromosome 3, and rearrangement of chromosome 3p could be causally involved with the amplification of MT genes in Cdr hamster cell lines.
Association of high rate of recombination with amplification of dominant selectable gene in human cells
TLDR
Cell DNA sequences near the integrated neogene may promote this recombination, and inclusion of this cell DNA in the initial tandem duplication might then explain the high rate of duplication and deletion observed in the region of the neogene in the RS-4 subclone.
Influence of cellular sequences on instability of plasmid integration sites in human cells
  • J. Murnane
  • Biology
    Somatic cell and molecular genetics
  • 1990
TLDR
DNA sequences that promote high rates of recombination are investigated by analyzing rare unstable plasmid integration sites in simian virus 40-transformed human fibroblasts, finding that a complex combination of sequences is involved, possibly within both the plasmids and cell DNA.
Amplification and Molecular Cloning of Transfected Genes
TLDR
The identification and cloning of cellular oncogenes, a major breakthrough in the past few years, was an achievement that may not have been possible or have occurred as swiftly without the ability to transfer DNA into mammalian cells and isolate transfectants.
Formation of an inverted duplication can be an initial step in gene amplification
TLDR
Molecular analysis of the integration site in transformant L46 revealed that the donated genes were at the center of an inverted duplication which spanned more than 70 kilobase pairs and consisted largely of host DNA.
...
...

References

SHOWING 1-10 OF 41 REFERENCES
The role of gene dosage and genetic transpositions in carcinogenesis
Analysis of chromosome translocations associated with B-cell derived tumours and studies of chromosome-15 trisomy in murine leukaemia support the theory, emerging from recent work on tumour viruses,…
The cloning and reintroduction into animal cells of a functional CAD gene, a dominant amplifiable genetic marker
Evolution of chromosomal regions containing transfected and amplified dihydrofolate reductase sequences
TLDR
It is proposed that integration of DNA may disrupt telomeric structures and facilitate the formation of dicentric chromosomes, which may then undergo bridge breakage-fusion cycles.
Transforming DNA integrates into the host chromosome
Single-copy and amplified CAD genes in Syrian hamster chromosomes localized by a highly sensitive method for in situ hybridization.
Syrian hamster cells resistant to N-(phosphonacetyl)-L-aspartate (PALA), a specific inhibitor of the aspartate transcarbamylase activity of the multifunctional protein CAD, overproduce this protein…
DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells.
TLDR
The feasibility of transforming mouse cells deficient in adenine phosphoribosyltransferase to the aprt+ phenotype by means of DNA-mediated gene transfer is demonstrated.
Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(phosphonacetyl)-L-aspartate-resistant hamster cells.
TLDR
Restriction patterns were analyzed by a new method in which fragments of DNA are transferred from agarose gels to diazo paper with a high efficiency which is independent of size, and indicated that part of this difference is attributable to intervening sequences in the CAD gene.
Structure of the gene for CAD, the multifunctional protein that initiates UMP synthesis in Syrian hamster cells
Two adjacent fragments of genomic DNA spanning the gene for CAD, which encodes the first three enzymes of UMP biosynthesis, were cloned from a mutant Syrian hamster cell line containing multiple…
Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line.
TLDR
Methotrexate-resistant Chinese hamster ovary cells selected for high resistance by progressive increments of methotrexate in the culture medium have levels of dihydrofolate reductase that are 200 times that of sensitive cells and a corresponding increase in the number of copies of the diHydrofolATE reduct enzyme gene.
Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae
TLDR
The frequency of unequal crossing over, as measured by the deletion or duplication of an inserted genetic marker (LEU2), is sufficient to maintain the sequence homogeneity of the rDNA repeat units.
...
...