Expression of Fragile Sites Triggers Intrachromosomal Mammalian Gene Amplification and Sets Boundaries to Early Amplicons

摘要: Drug-selected intrachromosomal gene amplification by breakage-fusion-bridge (BFB) cycles is well documented in mammalian cells, but factors governing this mechanism are not clear. Here, we show that only some clastogenic drugs induce drug resistance through amplification. We strictly correlate triggering of BFB to induction fragile site expression. demonstrate a dual role for sites amplification: telomeric the selected involved initiation, while centromeric defines size and organization early amplified units. The positions relative boundaries amplicons found human cancers support hypothesis play key at least oncogenes during tumor progression.