Cell cycle-dependent formation of Cdc45-Claspin complexes in human cells is compromized by UV-mediated DNA damage

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Title: Cell cycle-dependent formation of Cdc45-Claspin complexes in human cells is compromized by UV-mediated DNA damage
Authors: Broderick, Ronan
Rainey, Michael D.
Santocanale, Corrado
et al.
Permanent link: http://hdl.handle.net/10197/5053
Date: 27-Aug-2013
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.
Type of material: Journal Article
Publisher: Wiley Blackwell (Blackwell Publishing)
Copyright (published version): 2013 Wiley Blackwell (Blackwell Publishing)
Keywords: Cdc45;claspin;DNA damage response;DNA replication;intra-S-phase checkpoint
DOI: 10.1111/febs.12465
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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