Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex.
EMBO J
; 38(7)2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30782962
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Cromossômicas não Histona
/
Proteínas Serina-Treonina Quinases
/
Cinetocoros
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Proteínas de Ciclo Celular
/
Proteína de Ligação a Regiões Ricas em Polipirimidinas
/
Pontos de Checagem da Fase M do Ciclo Celular
/
Proteínas Associadas aos Microtúbulos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2019
Tipo de documento:
Article