Cell cycle-dependent formation of Cdc45-Claspin complexes in human cells is compromized by UV-mediated DNA damage
Rainey, Michael D.
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Broderick, Ronan, Rainey, Michael D., Santocanale, Corrado, & Nasheuer, Heinz P. (2013). Cell cycle-dependent formation of Cdc45–Claspin complexes in human cells is compromized by UV-mediated DNA damage. The FEBS Journal, 280(19), 4888-4902. doi:https://doi.org/10.1111/febs.12465
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 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.Structured digital abstract Clapsin physically interacts with Cdc45 by anti bait coimmunoprecipitation (View interaction) Cdc45 physically interacts with RPA32, Clapsin and p125 Pol delta by pull down (View interaction) Cdc45 physically interacts with RPA32 by pull down (View interaction) Cdc45 physically interacts with Clapsin by pull down (View interaction) Cdc45 physically interacts with Clapsin and RPA32 by pull down (View interaction) RPA32 physically interacts with Cdc45 by anti bait coimmunoprecipitation (View interaction)
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