Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation

Gang Zhang; Blanca Lopez Mendez; Garry G Sedgwick; Jakob Nilsson

doi:10.1038/ncomms12256

Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation

Gang Zhang, Blanca Lopez Mendez, Garry G Sedgwick, Jakob Nilsson

18 Citations (Scopus)

Abstract

The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore-microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.

Original language	English
Article number	12256
Journal	Nature Communications
Volume	7
Pages (from-to)	1-12
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms12256
Publication status	Published - 26 Jul 2016

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title = "Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation",

abstract = "The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore-microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.",

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AU - Zhang, Gang

AU - Mendez, Blanca Lopez

AU - Sedgwick, Garry G

AU - Nilsson, Jakob

PY - 2016/7/26

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N2 - The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore-microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.

AB - The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore-microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3.

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DO - 10.1038/ncomms12256

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JO - Nature Communications

JF - Nature Communications

M1 - 12256

ER -

Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation

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