Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex
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Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex. / Zhang, Gang; Kruse, Thomas; Guasch Boldú, Claudia; Garvanska, Dimitriya H; Coscia, Fabian; Mann, Matthias; Barisic, Marin; Nilsson, Jakob.
In: E M B O Journal, Vol. 38, No. 7, e100977, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex
AU - Zhang, Gang
AU - Kruse, Thomas
AU - Guasch Boldú, Claudia
AU - Garvanska, Dimitriya H
AU - Coscia, Fabian
AU - Mann, Matthias
AU - Barisic, Marin
AU - Nilsson, Jakob
N1 - © 2019 The Authors.
PY - 2019
Y1 - 2019
N2 - Kinetochore localized Mad1 is essential for generating a "wait anaphase" signal during mitosis, hereby ensuring accurate chromosome segregation. Inconsistent models for the function and quantitative contribution of the two mammalian Mad1 kinetochore receptors: Bub1 and the Rod-Zw10-Zwilch (RZZ) complex exist. By combining genome editing and RNAi, we achieve penetrant removal of Bub1 and Rod in human cells, which reveals that efficient checkpoint signaling depends on the integrated activities of these proteins. Rod removal reduces the proximity of Bub1 and Mad1, and we can bypass the requirement for Rod by tethering Mad1 to kinetochores or increasing the strength of the Bub1-Mad1 interaction. We find that Bub1 has checkpoint functions independent of Mad1 localization that are supported by low levels of Bub1 suggesting a catalytic function. In conclusion, our results support an integrated model for the Mad1 receptors in which the primary role of RZZ is to localize Mad1 at kinetochores to generate the Mad1-Bub1 complex.
AB - Kinetochore localized Mad1 is essential for generating a "wait anaphase" signal during mitosis, hereby ensuring accurate chromosome segregation. Inconsistent models for the function and quantitative contribution of the two mammalian Mad1 kinetochore receptors: Bub1 and the Rod-Zw10-Zwilch (RZZ) complex exist. By combining genome editing and RNAi, we achieve penetrant removal of Bub1 and Rod in human cells, which reveals that efficient checkpoint signaling depends on the integrated activities of these proteins. Rod removal reduces the proximity of Bub1 and Mad1, and we can bypass the requirement for Rod by tethering Mad1 to kinetochores or increasing the strength of the Bub1-Mad1 interaction. We find that Bub1 has checkpoint functions independent of Mad1 localization that are supported by low levels of Bub1 suggesting a catalytic function. In conclusion, our results support an integrated model for the Mad1 receptors in which the primary role of RZZ is to localize Mad1 at kinetochores to generate the Mad1-Bub1 complex.
U2 - 10.15252/embj.2018100977
DO - 10.15252/embj.2018100977
M3 - Journal article
C2 - 30782962
VL - 38
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 7
M1 - e100977
ER -
ID: 214021997