ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
Nat Cell Biol
; 8(1): 37-45, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16327781
ABSTRACT
It is generally thought that the DNA-damage checkpoint kinases, ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), work independently of one another. Here, we show that ATM and the nuclease activity of meiotic recombination 11 (Mre11) are required for the processing of DNA double-strand breaks (DSBs) to generate the replication protein A (RPA)-coated ssDNA that is needed for ATR recruitment and the subsequent phosphorylation and activation of Chk1. Moreover, we show that efficient ATM-dependent ATR activation in response to DSBs is restricted to the S and G2 cell cycle phases and requires CDK kinase activity. Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Ciclo Celular
/
Proteínas Serina-Treonina Quinases
/
Proteínas de Ciclo Celular
/
Proteínas Supressoras de Tumor
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article