ATM-dependent phosphorylation of the checkpoint clamp regulates repair pathways and maintains genomic stability.
Cell Cycle
; 11(9): 1796-803, 2012 May 01.
Article
em En
| MEDLINE
| ID: mdl-22453082
ABSTRACT
Upon genotoxic stress and during normal S phase, ATM phosphorylates the checkpoint clamp protein Rad9 in a manner that depends on Ser272. Ser272 is the only known ATM-dependent phosphorylation site in human Rad9. However, Ser272 phosphorylation is not required for survival or checkpoint activation after DNA damage. The physiological function of Ser272 remains elusive. Here, we show that ATM-dependent Rad9(Ser272) phosphorylation requires the MRN complex and controls repair pathways. Furthermore, the mutant cells accumulate large numbers of chromosome breaks and induce gross chromosomal rearrangements. Our findings establish a new and unexpected role for ATM it phosphorylates the checkpoint clamp in order to control repair pathways, thereby maintaining genomic integrity during unperturbed cell cycle and upon DNA damage.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
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Proteínas Supressoras de Tumor
/
Instabilidade Genômica
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Proteínas de Ligação a DNA
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Pontos de Checagem do Ciclo Celular
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos