Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells.
We have utilized a dihydrofolate reductase (DHFR) probe in combination with selected probes from other positions along the 2q chromosome arm in a two-color fluorescence in situ hybridization analysis of early DHFR gene amplification events in CHO cells. These studies show clearly that the most frequent initiating event is the formation of a giant inverted duplication, resulting from chromosome breakage and terminal fusion or a reverse unequal sister chromatid exchange. The dicentric chromosomes thus formed initiate bridge/breakage/fusion cycles that appear to mediate subsequent amplification steps to higher copy number.
Ma
C
C
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville 22908.
Martin
S
S
Trask
B
B
Hamlin
J L
JL
D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D007446:Chromosome Inversion; D006224:Cricetinae; D003412:Cricetulus; D005784:Gene Amplification / Q000235:genetics*; D015698:Genomic Library; D017404:In Situ Hybridization, Fluorescence; D012854:Sister Chromatid Exchange; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D013762:Tetrahydrofolate Dehydrogenase