Correcting improper chromosome–spindle attachments during cell division

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Abstract
For accurate segregation of chromosomes during cell division, microtubule fibres must attach sister kinetochores to opposite poles of the mitotic spindle (bi-orientation). Aurora kinases are linked to oncogenesis1 and have been implicated in the regulation of chromosome–microtubule attachments2. Although loss of Aurora kinase activity causes an accumulation of mal-orientated chromosomes in dividing cells3,4, it is not known how the active kinase corrects improper chromosome attachments. The use of reversible small-molecule inhibitors allows activation of protein function in living vertebrate cells with temporal control. Here we show that by removal of small-molecule inhibitors, controlled activation of Aurora kinase during mitosis can correct chromosome attachment errors by selective disassembly of kinetochore–microtubule fibres, rather than by alternative mechanisms involving initial release of microtubules from either kinetochores or spindle poles5,6,7. Observation of chromosomes and microtubule dynamics with real-time high-resolution microscopy showed that mal-orientated, but not bi-orientated, chromosomes move to the spindle pole as both kinetochore–microtubule fibres shorten, followed by alignment at the metaphase plate. Our results provide direct evidence for a mechanism required for the maintenance of genome integrity during cell division.