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Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint

Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint
Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint
The kinetochore is a dynamic multiprotein complex assembled at the centromere in mitosis. Exactly how the structure of the kinetochore changes during mitosis and how its individual components contribute to chromosome segregation is largely unknown. Here we have focused on the contribution of the Mis12 complex to kinetochore assembly and function throughout mitosis in Drosophila. We show that despite the sequential kinetochore recruitment of Mis12 complex subunits Mis12 and Nsl1, the complex acts as a single functional unit. mis12 and nsl1 mutants show strikingly similar developmental and mitotic defects in which chromosomes are able to congress at metaphase, but their anaphase movement is strongly affected. While kinetochore association of Ndc80 absolutely depends on both Mis12 and Nsl1, BubR1 localization shows only partial dependency. In the presence of residual centromeric BubR1 the checkpoint still responds to microtubule depolymerization but is significantly weaker. These observations point to a complexity of the checkpoint response that may reflect subpopulations of BubR1 associated with residual kinetochore components, the core centromere, or elsewhere in the cell. Importantly our results indicate that core structural elements of the inner plate of the kinetochore have a greater contribution to faithful chromosome segregation in anaphase than in earlier stages of mitosis.
1943-2631
131-140
Venkei, Zsolt
0df721fd-a3e7-4360-94e2-8470bd03f487
Przewloka, Marcin
9b25e73c-ec15-43df-a5a4-ac9574bb20ab
Glover, David M.
cca9cd19-3e1e-4906-b418-41876c1f9c61
Venkei, Zsolt
0df721fd-a3e7-4360-94e2-8470bd03f487
Przewloka, Marcin
9b25e73c-ec15-43df-a5a4-ac9574bb20ab
Glover, David M.
cca9cd19-3e1e-4906-b418-41876c1f9c61

Venkei, Zsolt, Przewloka, Marcin and Glover, David M. (2011) Drosophila Mis12 complex acts as a single functional unit essential for anaphase chromosome movement and a robust spindle assembly checkpoint. Genetics, 187 (1), 131-140. (doi:10.1534/genetics.110.119628). (PMID:20980244)

Record type: Article

Abstract

The kinetochore is a dynamic multiprotein complex assembled at the centromere in mitosis. Exactly how the structure of the kinetochore changes during mitosis and how its individual components contribute to chromosome segregation is largely unknown. Here we have focused on the contribution of the Mis12 complex to kinetochore assembly and function throughout mitosis in Drosophila. We show that despite the sequential kinetochore recruitment of Mis12 complex subunits Mis12 and Nsl1, the complex acts as a single functional unit. mis12 and nsl1 mutants show strikingly similar developmental and mitotic defects in which chromosomes are able to congress at metaphase, but their anaphase movement is strongly affected. While kinetochore association of Ndc80 absolutely depends on both Mis12 and Nsl1, BubR1 localization shows only partial dependency. In the presence of residual centromeric BubR1 the checkpoint still responds to microtubule depolymerization but is significantly weaker. These observations point to a complexity of the checkpoint response that may reflect subpopulations of BubR1 associated with residual kinetochore components, the core centromere, or elsewhere in the cell. Importantly our results indicate that core structural elements of the inner plate of the kinetochore have a greater contribution to faithful chromosome segregation in anaphase than in earlier stages of mitosis.

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More information

Accepted/In Press date: 21 October 2010
Published date: 1 January 2011
Organisations: Molecular and Cellular, Centre for Biological Sciences

Identifiers

Local EPrints ID: 393863
URI: http://eprints.soton.ac.uk/id/eprint/393863
ISSN: 1943-2631
PURE UUID: b6deb9cb-d13c-4ce6-8c1b-f0859567599d
ORCID for Marcin Przewloka: ORCID iD orcid.org/0000-0002-0329-9162

Catalogue record

Date deposited: 13 May 2016 15:43
Last modified: 03 Dec 2019 01:32

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