Phosphoproteomics reveals distinct modes of Mec1/ATR signaling during DNA replication.
Mol Cell
; 57(6): 1124-1132, 2015 Mar 19.
Article
en En
| MEDLINE
| ID: mdl-25752575
ABSTRACT
The Mec1/Tel1 kinases (human ATR/ATM) play numerous roles in the DNA replication stress response. Despite the multi-functionality of these kinases, studies of their in vivo action have mostly relied on a few well-established substrates. Here we employed a combined genetic-phosphoproteomic approach to monitor Mec1/Tel1 signaling in a systematic, unbiased, and quantitative manner. Unexpectedly, we find that Mec1 is highly active during normal DNA replication, at levels comparable or higher than Mec1's activation state induced by replication stress. This "replication-correlated" mode of Mec1 action requires the 9-1-1 clamp and the Dna2 lagging-strand factor and is distinguishable from Mec1's action in activating the downstream kinase Rad53. We propose that Mec1/ATR performs key functions during ongoing DNA synthesis that are distinct from their canonical checkpoint role during replication stress.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Saccharomyces cerevisiae
/
Proteómica
/
Péptidos y Proteínas de Señalización Intracelular
/
Replicación del ADN
/
Proteínas Proto-Oncogénicas c-ets
Límite:
Humans
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos