title: Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity.
abstract: When DNA topoisomerase II (topo II) activity is inhibited with a non-DNA-damaging topo II inhibitor (ICRF-193), mammalian cells become checkpoint arrested in G2-phase. In this study, we analyzed chromosome structure in cells that bypassed this checkpoint. We observed a novel type of chromosome aberration, which we call omega-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.
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Giménez-Abián
authors.forename: D J
authors.initials: DJ
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Devlin
authors.forename: M I
authors.initials: MI
authors.lastname: Giménez-Abián
authors.forename: C
authors.initials: C
authors.lastname: De la Torre
authors.forename: R T
authors.initials: RT
authors.lastname: Johnson
authors.forename: A M
authors.initials: AM
authors.lastname: Mullinger
authors.forename: C S
authors.initials: CS
authors.lastname: Downes
mesh_terms: D000818:Animals; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D054659:Diketopiperazines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008322:Mammals; D008938:Mitosis; D010879:Piperazines / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
chemical_list: D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D004250:DNA Topoisomerases, Type II