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Reference - PMID:26258632 - Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore.

Reference summary

PubMed ID
PMID:26258632
Title
Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore.
Authors
Akera T, Goto Y, Sato M, Yamamoto M, Watanabe Y
Citation
Nat Cell Biol 2015 Sep;17(9):1124-33
Publication year
2015
Abstract
For proper partitioning of genomes in mitosis, all chromosomes must be aligned at the spindle equator before the onset of anaphase. The spindle assembly checkpoint (SAC) monitors this process, generating a 'wait anaphase' signal at unattached kinetochores of misaligned chromosomes. However, the link between SAC activation and chromosome alignment is poorly understood. Here we show that Mad1, a core SAC component, plays a hitherto concealed role in chromosome alignment. Protein-protein interaction screening revealed that fission yeast Mad1 binds the plus-end-directed kinesin-5 motor protein Cut7 (Eg5 homologue), which is generally thought to promote spindle bipolarity. We demonstrate that Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator. Similarly, human Mad1 recruits another kinetochore motor CENP-E, revealing that Mad1 is the conserved dual-function protein acting in SAC activation and chromosome gliding. Our results suggest that the mitotic checkpoint has co-evolved with a mechanism to drive chromosome congression.

Annotation

GO biological process

GO:0099606 - microtubule plus-end directed mitotic chromosome migration

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GO cellular component

GO:0000776 - kinetochore

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GO:0044732 - mitotic spindle pole body

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GO molecular function

GO:0005515 - protein binding

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Single locus phenotype

FYPO:0000030 - abnormal mitotic chromosome congression

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FYPO:0008164 - abnormal protein localization to kinetochore during mitotic M phase

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FYPO:0005220 - abnormal protein oligomerization

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FYPO:0004318 - abolished mitotic spindle assembly checkpoint

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FYPO:0000705 - abolished protein-protein interaction

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FYPO:0005211 - decreased protein localization to mitotic spindle pole body during anaphase

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FYPO:0000276 - monopolar mitotic spindle

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FYPO:0003762 - normal mitotic spindle assembly checkpoint

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FYPO:0005042 - normal protein localization to kinetochore

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FYPO:0005212 - normal protein localization to kinetochore during mitotic prometaphase

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FYPO:0002901 - normal protein localization to kinetochore during vegetative growth

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FYPO:0002563 - normal protein localization to nuclear periphery

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FYPO:0000069 - resistance to thiabendazole

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FYPO:0000091 - sensitive to thiabendazole

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FYPO:0005069 - unequal mitotic sister chromatid segregation following normal mitosis

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Subunit composition

PBO:0015212 - homomeric(2)

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PBO:0015242 - homomeric(4)

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