An ATM-Chk2-INCENP pathway activates the abscission checkpoint.
J Cell Biol
; 220(2)2021 02 01.
Article
en En
| MEDLINE
| ID: mdl-33355621
During cell division, in response to chromatin bridges, the chromosomal passenger complex (CPC) delays abscission to prevent chromosome breakage or tetraploidization. Here, we show that inhibition of ATM or Chk2 kinases impairs CPC localization to the midbody center, accelerates midbody resolution in normally segregating cells, and correlates with premature abscission and chromatin breakage in cytokinesis with trapped chromatin. In cultured human cells, ATM activates Chk2 at late midbodies. In turn, Chk2 phosphorylates human INCENP-Ser91 to promote INCENP binding to Mklp2 kinesin and CPC localization to the midbody center through Mklp2 association with Cep55. Expression of truncated Mklp2 that does not bind to Cep55 or nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission. In contrast, expression of phosphomimetic INCENP-Ser91D or a chimeric INCENP protein that is targeted to the midbody center rescues the abscission delay in Chk2-deficient or ATM-deficient cells. Furthermore, the Mre11-Rad50-Nbs1 complex is required for ATM activation at the midbody in cytokinesis with chromatin bridges. These results identify an ATM-Chk2-INCENP pathway that imposes the abscission checkpoint by regulating CPC midbody localization.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Cromosómicas no Histona
/
Transducción de Señal
/
Citocinesis
/
Puntos de Control del Ciclo Celular
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Proteínas de la Ataxia Telangiectasia Mutada
/
Quinasa de Punto de Control 2
Límite:
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Grecia
Pais de publicación:
Estados Unidos