Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation
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Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation. / Zhang, Gang; Mendez, Blanca Lopez; Sedgwick, Garry G; Nilsson, Jakob.
In: Nature Communications, Vol. 7, 12256, 2016, p. 1-12.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation
AU - Zhang, Gang
AU - Mendez, Blanca Lopez
AU - Sedgwick, Garry G
AU - Nilsson, Jakob
PY - 2016
Y1 - 2016
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.
KW - Journal Article
U2 - 10.1038/ncomms12256
DO - 10.1038/ncomms12256
M3 - Journal article
C2 - 27457023
VL - 7
SP - 1
EP - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 12256
ER -
ID: 164181889