ICRF-193, a catalytic inhibitor of DNA topoisomerase II, delays the cell cycle progression from metaphase, but not from anaphase to the G1 phase in mammalian cells

Abstract We have shown previously that ICRF-193, a catalytic inhibitor of DNA topoisomerase II (topo II), delays cell cycle progression in HeLa S3 cells. We report here that the delay of the transition in M phase is observed when HeLa S3 cells were treated with ICRF-193 during metaphase, but not thereafter. ICRF-193 also delayed the degradation of cyclin B in the transition from M to G1 phase, while in Chinese hamster ovary (CHO) cells the drug did not delay the progression in M phase. Since HeLa S3 and CHO cells are `stringent' and `relaxed' in mitotic control, respectively, it is suggested that under topo II inhibition, the M phase checkpoint operates through an inability for chromosome segregation.