Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.

The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar...

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Main Authors: Michael D Blower, Tanya Daigle, Thom Kaufman, Gary H Karpen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-07-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.0020110&type=printable
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author Michael D Blower
Tanya Daigle
Thom Kaufman
Gary H Karpen
author_facet Michael D Blower
Tanya Daigle
Thom Kaufman
Gary H Karpen
author_sort Michael D Blower
collection DOAJ
description The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.
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spelling doaj-art-e3086ac090be4fe980c30a88c454218b2025-08-20T02:38:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042006-07-0127e11010.1371/journal.pgen.0020110Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.Michael D BlowerTanya DaigleThom KaufmanGary H KarpenThe centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.0020110&type=printable
spellingShingle Michael D Blower
Tanya Daigle
Thom Kaufman
Gary H Karpen
Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
PLoS Genetics
title Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
title_full Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
title_fullStr Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
title_full_unstemmed Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
title_short Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.
title_sort drosophila cenp a mutations cause a bubr1 dependent early mitotic delay without normal localization of kinetochore components
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.0020110&type=printable
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AT tanyadaigle drosophilacenpamutationscauseabubr1dependentearlymitoticdelaywithoutnormallocalizationofkinetochorecomponents
AT thomkaufman drosophilacenpamutationscauseabubr1dependentearlymitoticdelaywithoutnormallocalizationofkinetochorecomponents
AT garyhkarpen drosophilacenpamutationscauseabubr1dependentearlymitoticdelaywithoutnormallocalizationofkinetochorecomponents