Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity

When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-da maging topo TI inhibitor (ICRF-193), mammalian cells become checkpoint arre sted in G2-phase. In this study, we analyzed chromosome structure ill cells that bypassed this checkpoint. We observed a novel type of chromosome aber ration, which we call R-figures. These are entangled chromosome regions tha t indicate the persistence of catenations between nonhomologous sequences. The number of Omega-figures per cell increased sharply as cells evaded the transient block imposed by the topo II-dependent checkpoint, and the presen ce of caffeine (a checkpoint-evading agent) potentiated this increase. Thus , the removal of nonreplicative catenations, a process that promotes chromo some individualization in G2, may be monitored by the topo II-dependent che ckpoint in mammals.