Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity

When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo TI inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase. In this study, we analyzed chromosome structure ill cells that bypassed this checkpoint. We observed a novel type of chromosome aberration, which we call R-figures. These are entangled chromosome regions that 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 presence of caffeine (a checkpoint-evading agent) potentiated this increase. Thus, the removal of nonreplicative catenations, a process that promotes chromosome individualization in G2, may be monitored by the topo II-dependent checkpoint in mammals.