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Multiple roles for kinases in DNA replication
Ghislaine Henneke1, Stéphane Koundrioukoff, Ulrich Hübscher
1Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Abstract:
DNA replication is carried out by the replisome, which includes several proteins that are targets of cell-cycle-regulated kinases. The phosphorylation of proteins such as replication protein A, DNA polymerase-alpha and -delta, replication factor C, flap endonuclease 1 and DNA ligase I leads to their inactivation, suggesting that phosphorylation is important in the prevention of re-replication. Moreover, the phosphorylation of several of these replication proteins has been shown to block their association with the 'moving platform'-proliferating cell nuclear antigen. Therefore, phosphorylation seems to be a crucial regulator of replisome assembly and DNA replication, although its precise role in these processes remains to be clarified.