Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint
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Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. / Zhang, Gang; Lischetti, Tiziana; Hayward, Daniel G; Nilsson, Jakob.
In: Nature Communications, Vol. 6, 7162, 02.06.2015.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint
AU - Zhang, Gang
AU - Lischetti, Tiziana
AU - Hayward, Daniel G
AU - Nilsson, Jakob
PY - 2015/6/2
Y1 - 2015/6/2
N2 - The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of the Mad1-Mad2 complex that in more complex eukaryotes depends on the Rod-Zwilch-ZW10 (RZZ) complex. The kinetochore protein Zwint has been proposed to be the kinetochore receptor for RZZ, but here we show that Bub1 and not Zwint is required for RZZ recruitment. We find that the middle region of Bub1 encompassing a domain essential for SAC signalling contributes to RZZ localization. In addition, we show that a distinct region in Bub1 mediates kinetochore localization of BubR1 through direct binding, but surprisingly removal of this region increases checkpoint strength. Our work thus uncovers how Bub1 coordinates checkpoint signalling by distinct domains for RZZ and BubR1 recruitment and suggests that Bub1 localizes antagonistic checkpoint activities.
AB - The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of the Mad1-Mad2 complex that in more complex eukaryotes depends on the Rod-Zwilch-ZW10 (RZZ) complex. The kinetochore protein Zwint has been proposed to be the kinetochore receptor for RZZ, but here we show that Bub1 and not Zwint is required for RZZ recruitment. We find that the middle region of Bub1 encompassing a domain essential for SAC signalling contributes to RZZ localization. In addition, we show that a distinct region in Bub1 mediates kinetochore localization of BubR1 through direct binding, but surprisingly removal of this region increases checkpoint strength. Our work thus uncovers how Bub1 coordinates checkpoint signalling by distinct domains for RZZ and BubR1 recruitment and suggests that Bub1 localizes antagonistic checkpoint activities.
U2 - 10.1038/ncomms8162
DO - 10.1038/ncomms8162
M3 - Journal article
C2 - 26031201
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7162
ER -
ID: 139857893