Cell cycle-dependent formation of Cdc45-Claspin complexes in human cells is compromized by UV-mediated DNA damage.
FEBS J
; 280(19): 4888-902, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23910567
ABSTRACT
The replication factor Cdc45 has essential functions in the initiation and elongation steps of eukaryotic DNA replication and plays an important role in the intra-S-phase checkpoint. Its interactions with other replication proteins during the cell cycle and after intra-S-phase checkpoint activation are only partially characterized. In the present study, we show that the C terminal part of Cdc45 may mediate its interactions with Claspin. The interactions of human Cdc45 with the three replication factors Claspin, replication protein A and DNA polymerase δ are maximal during the S phase. Following UVC-induced DNA damage, Cdc45-Claspin complex formation is reduced, whereas the binding of Cdc45 to replication protein A is not affected. We also show that treatment of cells with UCN-01 and phosphatidylinositol 3-kinase-like kinase inhibitors does not rescue the UV-induced destabilization of Cdc45-Claspin interactions, suggesting that the loss of the interaction between Cdc45 and Claspin occurs upstream of ataxia telangiectasia and Rad 3-related activation in the intra-S-phase checkpoint.
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1
Base de dados:
MEDLINE
Assunto principal:
Ciclo Celular
/
Proteínas de Ciclo Celular
/
Proteínas Adaptadoras de Transdução de Sinal
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article