Premitotic chromosome individualization in mammalian cells depends on topoisomerase II activity

J. F. Giménez-Abián, D. J. Clarke, J. Devlin, M. I. Giménez-Abián, C. De La Torre, R. T. Johnson, A. M. Mullinger, C. S. Downes

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 Ω-figures. These are entangled chromosome regions that indicate the persistence of catenations between nonhomologous sequences. The number of Ω-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.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalChromosoma
Volume109
Issue number4
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
Acknowledgements. We would like to acknowledge Mr. J.L. Marcilla for his skillful photographic work and Ms. M. Carrascosa for technical assistance. We are most grateful to Dr. A. Creighton for the generous gift of ICRF-193, to the Cancer Research Campaign for support, as well as to the Dirección General de Invest-igación Científica y Técnica, from the Ministerio de Educación y Cultura, Spain (Projects PB94-0167 and PB96-0909) and to the European Union (Project BIO4-CT96-0275). We also thank the Comunidad Autónoma de Madrid and EMBO for grants supporting J.F.G.A. and D.J.C., respectively.

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