Extrachromosomal double minutes and chromosomal homogeneously staining regions as probes for chromosome research

Abstract

Gene amplification in human cancer cells generates two cytogenetically identifiable structures: extrachromosomal double minutes (DMs) and the chromosomal homogeneously staining region (HSR). DMs are composed of autonomously replicating circular DNA of genomic origin, and they tell us about how the extrachromosomal elements may behave in the cells, how they were entrapped by the micronuclei and how they were eliminated from the cells. On the other hand, the episome model predicts that extrachromosomal elements excised from the chromosome arm might generate DMs, and the breakage-fusion-bridge (BFB) cycle model explains the generation of the HSR. In accordance with this, a plasmid bearing a mammalian replication initiation region (IR) and a matrix attachment region (MAR) mimics gene amplification and generates DMs and HSRs de novo. The IR/MAR gene amplification system extends our understanding on the mechanism of gene amplification and the behavior of amplified genes. Furthermore, the system may suggest the way how extrachromosomal elements in general may alter the chromosome architecture and function.