Background
Much of the work in identifying cdc genes was performed throughout the 1970’s and ‘80’s by Leland Hartwell, president and director of the Fred Hutchinson Cancer Research Center in Seattle. His work focused primarily on cdc28, which was shown to be responsible for initiating DNA replication. Additionally, he found that downstream cdc’s would not become active until the actions of upstream cdc’s were completed. Hartwell was rewarded for his hard work with the 2001 Nobel Prize for physiology (Pulverer 2001).
Function
Much of the research on cdc proteins has been performed with the yeast Saccharomyces cerevisiae, in which cdc6 interacts strongly with the origin recognition complex (ORC) during DNA replication. A comparable amount of research has also been done with the yeast Schizosaccharomyces pombe, in which cdc18 performs the same functions as cdc6. More specifically, cdc6 is a key component in the formation and stabilization of the prereplicative complex (pre-RC), which is responsible for loading minichromosome maintenance proteins (MCMs) and other initiator proteins onto DNA origins prior to replication. It is recruited by the ORC in late M or early G1 phase, and is believed to hydrolyze ATP (Vas 2001).
Experiments have also shown that cdc6 plays an important role in preventing rereplication. Cdc6 contains sites that can be phosphorylated by cdc2 kinase. When this occurs after the beginning of S phase, new pre-RCs cannot form, thus preventing DNA rereplication (Vas 2001). Phosphorylation leads to cdc6 degradation in yeasts, and nuclear exportation in humans.