Interaction of Chk1 with Treslin negatively regulates the initiation of chromosomal DNA replication.
Mol Cell
; 57(3): 492-505, 2015 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-25557548
ABSTRACT
Treslin helps to trigger the initiation of DNA replication by promoting integration of Cdc45 into the replicative helicase. Treslin is a key positive-regulatory target of cell-cycle control mechanisms; activation of Treslin by cyclin-dependent kinase is essential for the initiation of replication. Here we demonstrate that Treslin is also a critical locus for negative regulatory mechanisms that suppress initiation. We found that the checkpoint-regulatory kinase Chk1 associates specifically with a C-terminal domain of Treslin (designated TRCT). Mutations in the TRCT domain abolish binding of Chk1 to Treslin and thereby eliminate Chk1-catalyzed phosphorylation of Treslin. Significantly, abolition of the Treslin-Chk1 interaction results in elevated initiation of chromosomal DNA replication during an unperturbed cell cycle, which reveals a function for Chk1 during a normal S phase. This increase is due to enhanced loading of Cdc45 onto potential replication origins. These studies provide important insights into how vertebrate cells orchestrate proper initiation of replication.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
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Xenopus laevis
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Proteínas de Ciclo Celular
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Proteínas de Xenopus
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Replicação do DNA
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article