The centromere geometry essential for keeping mitosis error free is controlled by spindle forces

Accurate segregation of chromosomes, essential for the stability of the genome, depends on 'bi-orientation'-simultaneous attachment of each individual chromosome to both poles of the mitotic spindle. On bi-oriented chromosomes, kinetochores (macromolecular complexes that attach the chromos...

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Bibliographic Details
Published in:Nature 2007-11, Vol.450 (7170), p.745-749
Main Authors: Kapoor, Tarun M, Khodjakov, Alexey, Lon arek, Jadranka, Kisurina-Evgenieva, Olga, Vinogradova, Tatiana, Hergert, Polla, La Terra, Sabrina
Format: Article
Language:English
Subjects:
Animals
Cell cycle
Cell Line
Centromere - metabolism
Chromatids - drug effects
Chromatids - metabolism
Chromosome Segregation - drug effects
Chromosomes
Elastic properties
Female
Kinetochores - metabolism
Macropodidae
Mammals
Microtubules - physiology
Mitosis
Proteins
Pyrimidines - pharmacology
Spindle Apparatus - metabolism
Synteny
Thiones - pharmacology
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Summary:Accurate segregation of chromosomes, essential for the stability of the genome, depends on 'bi-orientation'-simultaneous attachment of each individual chromosome to both poles of the mitotic spindle. On bi-oriented chromosomes, kinetochores (macromolecular complexes that attach the chromosome to the spindle) reside on the opposite sides of the chromosome's centromere. In contrast, sister kinetochores shift towards one side of the centromere on 'syntelic' chromosomes that erroneously attach to one spindle pole with both sister kinetochores. Syntelic attachments often arise during spindle assembly and must be corrected to prevent chromosome loss. It is assumed that restoration of proper centromere architecture occurs automatically owing to elastic properties of the centromere. Here we test this assumption by combining laser microsurgery and chemical biology assays in cultured mammalian cells. We find that kinetochores of syntelic chromosomes remain juxtaposed on detachment from spindle microtubules. These findings reveal that correction of syntelic attachments involves an extra step that has previously been overlooked: external forces must be applied to move sister kinetochores to the opposite sides of the centromere. Furthermore, we demonstrate that the shape of the centromere is important for spindle assembly, because bipolar spindles do not form in cells lacking centrosomes when multiple chromosomes with juxtaposed kinetochores are present. Thus, proper architecture of the centromere makes an important contribution to achieving high fidelity of chromosome segregation.
ISSN:0028-0836
1476-4687
1476-4679
DOI:10.1038/nature06344