Analysis of CAD Gene Amplification Using a Combined Approach of Molecular Genetics and Cytogenetics

1984 ◽  
pp. 319-345 ◽  
Author(s):  
Geoffrey M. Wahl ◽  
Virginia Allen ◽  
Suzanne Delbruck ◽  
Walter Eckhart ◽  
Judy Meinkoth ◽  
...  
Keyword(s):  
Molecular Genetics ◽  
Gene Amplification ◽  
Combined Approach ◽  
Cad Gene

scholarly journals Structure of DNA formed in the first step of CAD gene amplification.

1986 ◽  
Vol 5 (9) ◽  
pp. 2115-2121 ◽  
Author(s):  
E. Giulotto ◽  
I. Saito ◽  
G.R. Stark
Keyword(s):  
Gene Amplification ◽  
Cad Gene

Induction of CAD gene amplification by restriction endonucleases in V79,B7 Chinese hamster cells

1989 ◽  
Vol 225 (1-2) ◽  
pp. 61-64 ◽  
Author(s):  
P. Cavolina ◽  
C. Agnese ◽  
A. Maddalena ◽  
G. Sciandrello ◽  
A. Di Leonardo
Keyword(s):  
Gene Amplification ◽  
Chinese Hamster ◽  
Restriction Endonucleases ◽  
Chinese Hamster Cells ◽  
Cad Gene

Chromosome rearrangements associated with CAD gene amplification. Experiments with cell hybrids

1992 ◽  
Vol 265 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Silvia Viaggi ◽  
Michael Nüsse ◽  
Laura Ottaggio ◽  
Stefania Bonatti
Keyword(s):  
Gene Amplification ◽  
Chromosome Rearrangements ◽  
Cell Hybrids ◽  
Cad Gene

scholarly journals MYC Abrogates p53-Mediated Cell Cycle Arrest in N-(Phosphonacetyl)-l-Aspartate-Treated Cells, Permitting CAD Gene Amplification

1998 ◽  
Vol 18 (1) ◽  
pp. 536-545 ◽  
Author(s):  
Olga B. Chernova ◽  
Michail V. Chernov ◽  
Yukihito Ishizaka ◽  
Munna L. Agarwal ◽  
George R. Stark
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Gene Amplification ◽  
Dna Breaks ◽  
Pyrimidine Nucleotides ◽  
Cycle Arrest ◽  
Dependent Cell ◽  
Cad Gene ◽  
Resistant Cells

ABSTRACT Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, “nonpermissive” REF52 cells do not develop resistance toN-(phosphonacetyl)-l-aspartate (PALA), an inhibitor of the synthesis of pyrimidine nucleotides, through amplification of cad, the target gene, but instead undergo protective, long-term, p53-dependent cell cycle arrest. Expression of exogenous MYC prevents this arrest and allows REF52 cells to proceed to mitosis when pyrimidine nucleotides are limiting. This results in DNA breaks, leading to cell death and, rarely, to cad gene amplification and PALA resistance. Pretreatment of REF52 cells with a low concentration of PALA, which slows DNA replication but does not trigger cell cycle arrest, followed by exposure to a high, selective concentration of PALA, promotes the formation of PALA-resistant cells in which the physically linked cad and endogenous N-myc genes are coamplified. The activated expression of endogenous N-myc in these pretreated PALA-resistant cells allows them to bypass the p53-mediated arrest that is characteristic of untreated REF52 cells. Our data demonstrate that two distinct events are required to form PALA-resistant REF52 cells: amplification ofcad, whose product overcomes the action of the drug, and increased expression of N-myc, whose product overcomes the PALA-induced cell cycle block. These paired events occur at a detectable frequency only when the genes are physically linked, ascad and N-myc are. In untreated REF52 cells overexpressing N-MYC, the level of p53 is significantly elevated but there is no induction of p21 waf1 expression or growth arrest. However, after DNA is damaged, the activated p53 executes rapid apoptosis in these REF52/N-myc cells instead of the long-term protective arrest seen in REF52 cells. The predominantly cytoplasmic localization of stabilized p53 in REF52/N-myc cells suggests that cytoplasmic retention may help to inactivate the growth-suppressing function of p53.

scholarly journals High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6

2001 ◽  
Vol 98 (24) ◽  
pp. 13802-13807 ◽  
Author(s):  
S. Chen ◽  
S. H. Bigner ◽  
P. Modrich
Keyword(s):  
Gene Amplification ◽  
Human Cells ◽  
High Rate ◽  
Cad Gene

scholarly journals Unstable and stable CAD gene amplification: importance of flanking sequences and nuclear environment in gene amplification.

1987 ◽  
Vol 7 (4) ◽  
pp. 1415-1424 ◽  
Author(s):  
J Meinkoth ◽  
A M Killary ◽  
R E Fournier ◽  
G M Wahl
Keyword(s):  
Mouse Chromosome ◽  
Gene Amplification ◽  
Mouse Cell ◽  
Cad Gene ◽  
Flanking Sequences ◽  
Mouse Cells ◽  
Nuclear Environment ◽  
Stable Cad ◽  
First Time ◽  
Degree Of Instability

We analyzed the amplification of the CAD gene in independently isolated N-(phosphonacetyl)-L-aspartate-resistant clones derived from single parental clones in two mouse cell lines. We report 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. These data are most consistent with the idea that the amplified unit in each clone consists of different flanking DNA and that such differences engender amplified sequences with unequal stability. We also introduced the mouse chromosome containing the CAD gene into hamster cells by microcell-mediated chromosome transfer to determine whether the propensity for unstable extrachromosomal amplification of the mouse CAD gene would prevail in the hamster cell nuclear environment. We report that the mouse CAD gene was amplified stably in expanded chromosomal regions in each of seven hybrids that were analyzed. This observation is consistent with the idea that the nuclear environment influences whether mutants containing intra- or extrachromosomally amplified sequences will be isolated.

Unstable and stable CAD gene amplification: importance of flanking sequences and nuclear environment in gene amplification

1987 ◽  
Vol 7 (4) ◽  
pp. 1415-1424
Author(s):  
J Meinkoth ◽  
A M Killary ◽  
R E Fournier ◽  
G M Wahl
Keyword(s):  
Mouse Chromosome ◽  
Gene Amplification ◽  
Mouse Cell ◽  
Cad Gene ◽  
Flanking Sequences ◽  
Mouse Cells ◽  
Nuclear Environment ◽  
Stable Cad ◽  
First Time ◽  
Degree Of Instability

We analyzed the amplification of the CAD gene in independently isolated N-(phosphonacetyl)-L-aspartate-resistant clones derived from single parental clones in two mouse cell lines. We report 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. These data are most consistent with the idea that the amplified unit in each clone consists of different flanking DNA and that such differences engender amplified sequences with unequal stability. We also introduced the mouse chromosome containing the CAD gene into hamster cells by microcell-mediated chromosome transfer to determine whether the propensity for unstable extrachromosomal amplification of the mouse CAD gene would prevail in the hamster cell nuclear environment. We report that the mouse CAD gene was amplified stably in expanded chromosomal regions in each of seven hybrids that were analyzed. This observation is consistent with the idea that the nuclear environment influences whether mutants containing intra- or extrachromosomally amplified sequences will be isolated.

Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells

1988 ◽  
Vol 199 (1) ◽  
pp. 111-121
Author(s):  
L. Ottaggio ◽  
C. Agnese ◽  
S. Bonatti ◽  
P. Cavolina ◽  
A. De Ambrosis ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Chromosome Aberrations ◽  
Cultured Cells ◽  
Chinese Hamster ◽  
Cad Gene

Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells

1988 ◽  
Vol 199 (1) ◽  
pp. 111-121 ◽  
Author(s):  
L. Ottaggio ◽  
C. Agnese ◽  
S. Bonatti ◽  
P. Cavolina ◽  
A. De Ambrosis ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Chromosome Aberrations ◽  
Cultured Cells ◽  
Chinese Hamster ◽  
Cad Gene
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