Effect of Genomic Position on Amplification of the DFR1 Gene in Saccharomyces Cerevisiae

Abstract

Among the best studied examples of DNA amplification, as a response to drug selection, is the increased DHFR gene copy number observed in tumor cells resistant to methotrexate (MTX)^1,2,. In spite of numerous studies into the mechanism of DHFR gene amplification in a variety of cell types, we do not yet have a detailed understanding of the molecular events which initiate the amplification process. Moreover, in spite of a relative wealth of information about the distribution and arrangement of amplicons observed in MTX^R cells, we know very little about endogenous factors which affect the frequency of DHFR amplification-nor do we understand, at the molecular level, the process of resolution of early events into the final amplicon structures observed in drug-resistant cells.