ABSTRACT
Gene amplification is commonly observed in malignant cells and in drug-resistant cell lines. It is a dynamic process in which the structures generated early are altered during cell propagation or drug selection. Amplified sequences are often detected as paired acentric circular structures called double minute chromosomes, or as expanded chromosomal regions. To investigate the molecular mechanisms governing the amplification process, the authors constructed a model system consisting of an integrated SV40 genome in virally transformed Chinese hamster cells. Damaged template, modified DNA, nicks, triple-helix structures, sequences with specific conformation, and protein–DNA complexes might arrest the advancement of the replication fork and could lead to U-turn replication. The newly generated hairpin structures might recombine into the chromosome, yielding chromosomally associated inverted repeat duplications.
