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. 
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.
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.
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