Distinctive chromosomal structures are formed very early in the amplification of CAD genes in Syrian hamster cells

Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells.

“…A variety of mechanisms appears to mediate the amplification of specific genes, even within a population of cells (reviewed by Schimke, 1988;Stark et al, 1989;Smith et al, 1990). The initial step(s) of gene amplification have been difficult to define.…”

“…Several studies have used in situ hybridization/fluorescent techniques to identify very early amplification structures. These studies indicate that gene amplification can be mediated by either intra-or interchromosomal recombination events, such as sister chromatid exchange (Trask and Hamlin, 1989;Smith et al, 1990), or by extrachromosomal circular DNA intermediates (Wahl, 1989;Ruiz and Wahl, 1990;Windle et al, 1991).…”

Inefficient growth arrest in response to dNTP starvation stimulates gene amplification through bridge-breakage-fusion cycles.

“…The experiments were performed as described by Smith et al (1990). Briefly, mitotic metaphase spreads were treated with RNAse A in 2x SSC at 37°C for 1 h, dehydrated through an alcohol series, and dried.…”

“…eutiogn erative drugs through gene amplification (for reviews, toward increasingly malignant phenotypes Cytoge-see Stark and Wahl, 1984;Schimke, 1988; netic and molecular evidence of amplification has 1989; Windle and Wahl, 1992;Stark, 1993). usually appears as ladder-like repeats containing the selected gene, usually located on the same chromosome arm that normally carries a single copy of the gene (Trask and Hamlin, 1989;Smith et al, 1990;Toledo et al, 1992Toledo et al, , 1993. Analyses of very early events in N-phosphonacetyl-L-aspartate (PALA)Y-resistant BHK cells and in coformycin-resistant Chinese hamster cells has revealed a high proportion of dicentric chromosomes containing amplifications of the target gene (Smith et al, 1992;Toledo et al, 1992).…”

Multiple mechanisms of N -phosphonacetyl- l -aspartate resistance in human cell lines: Carbamyl- P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged

“…In rodent cells, amplified genes are often seen as ladder-like repeats, usually on the same chromosome arm that carries a single copy of the gene in wild-type cells (1)(2)(3)(4). The presence of dicentric chromosomes in newly selected cells (3,5) has led to the conclusion that chromosome breakage or telomere fusion initiates bridge-breakage-fusion cycles, leading to formation of dicentric sister chromatids, dicentric chromosomes, and eventually the amplified structures observed (reviewed in ref.…”