The dynamics of acentric chromosomes in cancer cells revealed by GFP-basedchromosome labeling strategies

Autonomous replicons, such as viral episomes and oncogene containing double minute chromosomes (DMs), lack centromeres and consequently should be lost rapidly when the nuclear membrane breaks down at mitosis. Surprisingly, th ey are not. This raises the important question of the mechanisms that enabl e their efficient transmission to daughter cells. We review recent developm ents in GFP-based chromosome labeling strategies that enable real time anal yses using high resolution light microscopy to provide insights into this i ssue. The results reveal that episomes and DMs both adhere to host chromoso mes, a process referred to as "chromosome tethering". Such association enab les acentric molecules to use the chromosomal centromere in trans, thereby achieving efficient transmission to daughter cells. This unique mechanism o i mitotic segregation also raises the possibility of developing a new class of anti-cancer drugs that work by selectively eliminating growth enhancing genes from cancer cells, (C) 2001 Wiley-Liss, Inc.