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 expressed before initiation of DNA replication and is thought to be essential for loading of the helicase onto origin DNA. The biochemical properties of the protein, however, are largely unknown. Using three archaeal homologues of Cdc6, it was found that the proteins are autophosphorylated on Ser residues. 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.

起始蛋白Cdc6（裂殖酵母中同源蛋白为Cdc18）在真核生物DNA复制起始过程中发挥关键作用。在酵母中，该蛋白于DNA复制起始前即已表达，且被认为对解旋酶装载至复制起始位点DNA的过程至关重要。不过，该蛋白的生化特性在很大程度上仍未被阐明。研究人员利用三种Cdc6的古菌同源蛋白开展实验，发现这些蛋白可在丝氨酸残基位点发生自磷酸化修饰。Cdc6的C端翼螺旋结构域可与DNA结合，这一相互作用显然可调控其自磷酸化反应。同时研究还发现酵母Cdc18同样具备自磷酸化活性，这表明Cdc6的这一功能可能在复制起始过程中发挥了广泛保守且不可或缺的作用。