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Correcting improper chromosome-spindle attachments during cell division.

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 oncogenesis and have been implicated in the regulation of chromosome-microtubule attachments. Although loss of Aurora kinase activity causes an accumulation of mal-orientated chromosomes in dividing cells, 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 poles. 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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Lampson MA,Renduchitala K,Khodjakov A,Kapoor TM

doi

10.1038/ncb1102

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

232-7

issue

3

eissn

1465-7392

issn

1476-4679

pii

ncb1102

journal_volume

6

pub_type

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