Autophosphorylation of archaeal Cdc6 homologues is regulated by DNA

The initiator protein Cdc6 (Cdc18 in fission yeast) plays an essential role in the initiation of eukaryotic DNA replication. In yeast the protein is e xpressed before initiation of DNA replication and is thought to be essentia l for loading of the helicase onto origin DNA. The biochemical properties o f the protein, however, are largely unknown. Using three archaeal homologue s of Cdc6, it was found that the proteins are autophosphorylated on Ser res idues. The winged-helix domain at the C terminus of Cdc6 interacts with DNA , which apparently regulates the autophosphorylation reaction. Yeast Cdc18 was also found to autophosphorylate, suggesting that this function of Cdc6 may play a widely conserved and essential role in replication initiation.