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 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 aberr...

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Bibliographic Details
Published in:Chromosoma 2000-07, Vol.109 (4), p.235-244
Main Authors: Giménez-Abián, J F, Clarke, D J, Devlin, J, Giménez-Abián, M I, De la Torre, C, Johnson, R T, Mullinger, A M, Downes, C S
Format: Article
Language:English
Subjects:
Animals
DNA Topoisomerases, Type II - metabolism
Enzyme Inhibitors - pharmacology
ICRF-193
Mammals
Mitosis
Piperazines - pharmacology
Proteins
Topoisomerase II Inhibitors
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Summary: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.
ISSN:0009-5915
1432-0886
DOI:10.1007/s004120000065