Small changes in phospho-occupancy at the kinetochore-microtubule interface drive mitotic fidelity.
J Cell Biol
; 221(9)2022 09 05.
Article
en En
| MEDLINE
| ID: mdl-35878017
ABSTRACT
Kinetochore protein phosphorylation promotes the correction of erroneous microtubule attachments to ensure faithful chromosome segregation during cell division. Determining how phosphorylation executes error correction requires an understanding of whether kinetochore substrates are completely (i.e., all-or-none) or only fractionally phosphorylated. Using quantitative mass spectrometry (MS), we measured phospho-occupancy on the conserved kinetochore protein Hec1 (NDC80) that directly binds microtubules. None of the positions measured exceeded â¼50% phospho-occupancy, and the cumulative phospho-occupancy changed by only â¼20% in response to changes in microtubule attachment status. The narrow dynamic range of phospho-occupancy is maintained, in part, by the ongoing phosphatase activity. Further, both Cdk1-Cyclin B1 and Aurora kinases phosphorylate Hec1 to enhance error correction in response to different types of microtubule attachment errors. The low inherent phospho-occupancy promotes microtubule attachment to kinetochores while the high sensitivity of kinetochore-microtubule attachments to small changes in phospho-occupancy drives error correction and ensures high mitotic fidelity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cinetocoros
/
Proteínas del Citoesqueleto
/
Microtúbulos
/
Mitosis
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2022
Tipo del documento:
Article