Src family kinases maintain the balance between replication stress and the replication checkpoint.
Cell Biol Int
; 40(1): 16-26, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26194897
ABSTRACT
Progression of DNA replication is tightly controlled by replication checkpoints to ensure the accurate and rapid duplication of genetic information. Upon replication stress, the replication checkpoint slows global DNA replication by inhibiting the late-firing origins and by slowing replication fork progression. Activation of the replication checkpoint has been studied in depth; however, little is known about the termination of the replication checkpoint. Here, we show that Src family kinases promote the recovery from replication checkpoints. shRNA knockdown of a Src family kinase, Lyn, and acute chemical inhibition of Src kinases prevented inactivation of Chk1 after removal of replication stress. Consistently, Src inhibition slowed resumption of DNA replication, after the removal of replication blocks. The effect of Src inhibition was not observed in the presence of an ATM/ATR inhibitor caffeine. These data indicate that Src kinases promote the resumption of DNA replication by suppressing ATR-dependent replication checkpoints. Surprisingly, the resumption of replication was delayed by caffeine. In addition, Src inhibition delayed recovery from replication fork collapse. We propose that Src kinases maintain the balance between replication stress and the activity of the replication checkpoint.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Quinases da Família src
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Replicação do DNA
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Pontos de Checagem do Ciclo Celular
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Proteínas Mutadas de Ataxia Telangiectasia
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article