Background information
The Cdc 34 gene represents a mammalian homolog of the group of yeast Cdc 34 genes required for the late G1 - S phase transition. A key negative regulator of mitosis, the protein kinase Wee 1, is degraded in a Cdc 34 dependent fashion in Xenopus egg extracts. This proteolysis event is required for a timely entrance into mitosis and is inhibited when DNA replication is blocked. Therefore, the DNA replication checkpoint can prevent mitosis by suppressing the proteolysis of Wee 1 during S phase. The human Cdc 34 gene is located on the far telomeric region of 19p13. Mutants in the gene Cdc 34 of the yeast Saccharomyces cerevisiae are defective in the transition from G1 to the S phase of the cell cycle. This gene was cloned and shown to encode a 295 residue protein that has substantial sequence similarity to yeast Rad6 protein required for a variety of cellular functions including DNA repair and was recently shown to encode a ubiquitin conjugating enzyme. When produced in Escherichia coli, the Cdc 34 gene product catalyzes the covalent attachment of ubiquitin to histones H2A and H2B in vitro, demonstrating that the Cdc 34 protein is another distinct member of the family of ubiquitin conjugating enzymes. The cell cycle function of Cdc 34 is thus likely to be mediated by the ubiquitin conjugating activity of its product.
