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 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.
Giménez-Abián
J F
JF
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Clarke
D J
DJ
Devlin
J
J
Giménez-Abián
M I
MI
De la Torre
C
C
Johnson
R T
RT
Mullinger
A M
AM
Downes
C S
CS
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
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